Bladder Cancer - Molecular Biology

Overview

A diverse range of different chromosomal abnormalities have been reported in bladder cancer cells. The most frequently detected genetic abnormality in transitional cell carcinoma (TCC) of bladder is LOH on chromosome 9.

Abnormalities in genes regulating cell cycle control are often seen in advanced bladder cancers, particularly mutations in TP53 and proteins of the G1 checkpoint, especially RB1, CDKN2A (p16) and cyclin D1 (CCND1).

Overexpression of p73 is also common in bladder cancers and some studies have shown that this is associated with disease progression. Differential mucin expression have also been reported in bladder cancers. However, there are conflicting reports about expression specific mucins; MUC1, MUC2 and MUC7.

Uroplakins (membrane proteins) are expressed in both normal and cancerous urothelium and can act as a marker for the detection of metastases and circulating TCC cells.

Gene-Environment Interactions: A number of studies have investigated genes that might modulate the susceptibility to bladder cancer associated with cigarette smoking. These include the NAT1, NAT2, and GSTM1 genes.

See also: Bladder Cancer - clinical resources (22)

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 08 August, 2015 using data from PubMed, MeSH and CancerIndex

Mutated Genes and Abnormal Protein Expression (299)

How to use this data tableClicking on the Gene or Topic will take you to a separate more detailed page. Sort this list by clicking on a column heading e.g. 'Gene' or 'Topic'.

GeneLocationAliasesNotesTopicPapers
TP53 17p13.1 P53, BCC7, LFS1, TRP53 -TP53 and Bladder Cancer
491
FGFR3 4p16.3 ACH, CEK2, JTK4, CD333, HSFGFR3EX -FGFR3 and Bladder Cancer
157
CDKN2A 9p21 ARF, MLM, P14, P16, P19, CMM2, INK4, MTS1, TP16, CDK4I, CDKN2, INK4A, MTS-1, P14ARF, P19ARF, P16INK4, P16INK4A, P16-INK4A Deletion
-CDKN2A deletion in Bladder Cancer
148
BIRC5 17q25 API4, EPR-1 -BIRC5 and Bladder Cancer
139
NAT2 8p22 AAC2, PNAT, NAT-2 -NAT2 and Bladder Cancer
137
GSTM1 1p13.3 MU, H-B, GST1, GTH4, GTM1, MU-1, GSTM1-1, GSTM1a-1a, GSTM1b-1b -GSTM1 and Bladder Cancer
128
TNF 6p21.3 DIF, TNFA, TNFSF2, TNF-alpha -TNF and Bladder Cancer
90
RB1 13q14.2 RB, pRb, OSRC, pp110, p105-Rb, PPP1R130 -RB1 and Bladder Cancer
70
GSTP1 11q13 PI, DFN7, GST3, GSTP, FAEES3, HEL-S-22 -GSTP1 and Bladder Cancer
55
CDKN1A 6p21.2 P21, CIP1, SDI1, WAF1, CAP20, CDKN1, MDA-6, p21CIP1 -CDKN1A Expression in Bladder Cancer
48
PPARG 3p25 GLM1, CIMT1, NR1C3, PPARG1, PPARG2, PPARgamma -PPARG and Bladder Cancer
44
PROC 2q13-q14 PC, APC, PROC1, THPH3, THPH4 -PROC and Bladder Cancer
41
XRCC1 19q13.2 RCC -XRCC1 and Bladder Cancer
40
CASP3 4q34 CPP32, SCA-1, CPP32B -CASP3 and Bladder Cancer
38
ERBB2 17q12 NEU, NGL, HER2, TKR1, CD340, HER-2, MLN 19, HER-2/neu -ERBB2 and Bladder Cancer
33
CD44 11p13 IN, LHR, MC56, MDU2, MDU3, MIC4, Pgp1, CDW44, CSPG8, HCELL, HUTCH-I, ECMR-III -CD44 and Bladder Cancer
33
KIT 4q12 PBT, SCFR, C-Kit, CD117 -KIT and Bladder Cancer
32
NAT1 8p22 AAC1, MNAT, NATI, NAT-1 -NAT1 and Bladder Cancer
30
AKT1 14q32.32 AKT, PKB, RAC, CWS6, PRKBA, PKB-ALPHA, RAC-ALPHA -AKT1 and Bladder Cancer
27
MTOR 1p36.2 FRAP, FRAP1, FRAP2, RAFT1, RAPT1 -MTOR and Bladder Cancer
27
PIK3CA 3q26.3 MCM, CWS5, MCAP, PI3K, CLOVE, MCMTC, p110-alpha -PIK3CA and Bladder Cancer
24
CDKN1B 12p13.1-p12 KIP1, MEN4, CDKN4, MEN1B, P27KIP1 -CDKN1B and Bladder Cancer
23
MUC1 1q21 EMA, MCD, PEM, PUM, KL-6, MAM6, MCKD, PEMT, CD227, H23AG, MCKD1, MUC-1, ADMCKD, ADMCKD1, CA 15-3, MUC-1/X, MUC1/ZD, MUC-1/SEC Overexpression
-MUC1 and Bladder Cancer
21
AR Xq12 KD, AIS, TFM, DHTR, SBMA, HYSP1, NR3C4, SMAX1, HUMARA -AR and Bladder Cancer
21
VEGFA 6p12 VPF, VEGF, MVCD1 -VEGF Expression in Bladder Cancer
21
NRAS 1p13.2 NS6, CMNS, NCMS, ALPS4, N-ras, NRAS1 -NRAS and Bladder Cancer
19
IL10 1q31-q32 CSIF, TGIF, GVHDS, IL-10, IL10A -Interleukin-10 and Bladder Cancer
18
FHIT 3p14.2 FRA3B, AP3Aase -FHIT and Bladder Cancer
17
H19 11p15.5 ASM, BWS, WT2, ASM1, PRO2605, D11S813E, LINC00008, NCRNA00008 -H19 and Bladder Cancer
17
CD82 11p11.2 R2, 4F9, C33, IA4, ST6, GR15, KAI1, SAR2, TSPAN27 -CD82 and Bladder Cancer
17
CDK4 12q14 CMM3, PSK-J3 -CDK4 and Bladder Cancer
14
CDKN2B 9p21 P15, MTS2, TP15, CDK4I, INK4B, p15INK4b -CDKN2B and Bladder Cancer
13
DAPK1 9q21.33 DAPK -DAPK1 and Bladder Cancer
13
EZH2 7q35-q36 WVS, ENX1, EZH1, KMT6, WVS2, ENX-1, EZH2b, KMT6A -EZH2 and Bladder Cancer
13
E2F3 6p22 E2F-3 -E2F3 and Bladder Cancer
12
FGFR2 10q26 BEK, JWS, BBDS, CEK3, CFD1, ECT1, KGFR, TK14, TK25, BFR-1, CD332, K-SAM -FGFR2 and Bladder Cancer
12
IGF2 11p15.5 IGF-II, PP9974, C11orf43 -IGF2 and Bladder Cancer
12
ERCC1 19q13.32 UV20, COFS4, RAD10 -ERCC1 and Bladder Cancer
11
FGFR1 8p11.23-p11.22 CEK, FLG, HH2, OGD, FLT2, KAL2, BFGFR, CD331, FGFBR, FLT-2, HBGFR, N-SAM, FGFR-1, HRTFDS, bFGF-R-1 -FGFR1 and Bladder Cancer
11
KRT20 17q21.2 K20, CD20, CK20, CK-20, KRT21 -KRT20 and Bladder Cancer
11
DAPK2 15q22.31 DRP1, DRP-1 -DAPK2 and Bladder Cancer
11
XIAP Xq25 API3, ILP1, MIHA, XLP2, BIRC4, IAP-3, hIAP3, hIAP-3 -XIAP and Bladder Cancer
10
GPX1 3p21.3 GPXD, GSHPX1 -GPX1 and Bladder Cancer
10
TGFA 2p13 TFGA -TGFA and Bladder Cancer
10
CLMP 11q24.1 ACAM, ASAM, CSBM, CSBS -CLMP and Bladder Cancer
9
FAS 10q24.1 APT1, CD95, FAS1, APO-1, FASTM, ALPS1A, TNFRSF6 -FAS and Bladder Cancer
9
TGFBR1 9q22 AAT5, ALK5, ESS1, LDS1, MSSE, SKR4, ALK-5, LDS1A, LDS2A, TGFR-1, ACVRLK4, tbetaR-I -TGFBR1 and Bladder Cancer
9
JUN 1p32-p31 AP1, AP-1, c-Jun -c-Jun and Bladder Cancer
9
KRT5 12q13.13 K5, CK5, DDD, DDD1, EBS2, KRT5A -KRT5 and Bladder Cancer
9
CCNB1 5q12 CCNB -CCNB1 and Bladder Cancer
9
VEGFC 4q34.3 VRP, Flt4-L, LMPH1D -VEGFC and Bladder Cancer
8
TERC 3q26 TR, hTR, TRC3, DKCA1, PFBMFT2, SCARNA19 -TERC and Bladder Cancer
8
AURKA 20q13 AIK, ARK1, AURA, BTAK, STK6, STK7, STK15, AURORA2, PPP1R47 -AURKA and Bladder Cancer
8
ICAM1 19p13.3-p13.2 BB2, CD54, P3.58 -ICAM1 and Bladder Cancer
8
NME1 17q21.3 NB, AWD, NBS, GAAD, NDKA, NM23, NDPKA, NDPK-A, NM23-H1 -NME1 and Bladder Cancer
8
TUBE1 6q21 TUBE, dJ142L7.2 -TUBE1 and Bladder Cancer
8
EPHX1 1q42.1 MEH, EPHX, EPOX, HYL1 -EPHX1 and Bladder Cancer
7
PDLIM4 5q31.1 RIL -PDLIM4 and Bladder Cancer
7
HLA-A 6p21.3 HLAA -HLA-A and Bladder Cancer
7
KRT7 12q13.13 K7, CK7, SCL, K2C7 -KRT7 and Bladder Cancer
7
FASLG 1q23 APTL, FASL, CD178, CD95L, ALPS1B, CD95-L, TNFSF6, APT1LG1 -FASLG and Bladder Cancer
7
TACC3 4p16.3 ERIC1, ERIC-1 -TACC3 and Bladder Cancer
7
EDNRB 13q22 ETB, ET-B, ETBR, ETRB, HSCR, WS4A, ABCDS, ET-BR, HSCR2 -EDNRB and Bladder Cancer
6
NOS2 17q11.2 NOS, INOS, NOS2A, HEP-NOS -NOS2 and Bladder Cancer
6
MAPK1 22q11.21 ERK, p38, p40, p41, ERK2, ERT1, ERK-2, MAPK2, PRKM1, PRKM2, P42MAPK, p41mapk, p42-MAPK -MAPK1 and Bladder Cancer
6
GAPDH 12p13 G3PD, GAPD, HEL-S-162eP -GAPDH and Bladder Cancer
6
CCR2 3p21.31 CKR2, CCR-2, CCR2A, CCR2B, CD192, CKR2A, CKR2B, CMKBR2, MCP-1-R, CC-CKR-2 -CCR2 and Bladder Cancer
6
STAG2 Xq25 SA2, SA-2, SCC3B, bA517O1.1 GWS
-STAG2 and Bladder Cancer
6
ARHGDIB 12p12.3 D4, GDIA2, GDID4, LYGDI, Ly-GDI, RAP1GN1, RhoGDI2 -ARHGDIB and Bladder Cancer
6
TEP1 14q11.2 TP1, TLP1, p240, TROVE1, VAULT2 -TEP1 and Bladder Cancer
5
BMI1 10p11.23 PCGF4, RNF51, FLVI2/BMI1 -BMI1 and Bladder Cancer
5
LGALS3 14q22.3 L31, GAL3, MAC2, CBP35, GALBP, GALIG, LGALS2 -LGALS3 and Bladder Cancer
5
BIRC7 20q13.3 KIAP, LIVIN, MLIAP, RNF50, ML-IAP -BIRC7 and Bladder Cancer
5
HPRT1 Xq26.1 HPRT, HGPRT -HPRT1 and Bladder Cancer
5
AKT2 19q13.1-q13.2 PKBB, PRKBB, HIHGHH, PKBBETA, RAC-BETA -AKT2 and Bladder Cancer
5
LARS 5q32 LRS, LEUS, LFIS, ILFS1, LARS1, LEURS, PIG44, RNTLS, HSPC192, hr025Cl -LARS and Bladder Cancer
5
TIMP2 17q25 DDC8, CSC-21K -TIMP2 and Bladder Cancer
5
ERCC6 10q11.23 CSB, CKN2, COFS, ARMD5, COFS1, RAD26, UVSS1 -ERCC6 and Bladder Cancer
5
RALA 7p15-p13 RAL -RALA and Bladder Cancer
5
HAS1 19q13.4 HAS -HAS1 and Bladder Cancer
4
EREG 4q13.3 ER -EREG and Bladder Cancer
4
MAGEA3 Xq28 HIP8, HYPD, CT1.3, MAGE3, MAGEA6 -MAGEA3 and Bladder Cancer
4
KLF4 9q31 EZF, GKLF -KLF4 and Bladder Cancer
4
GSTO1 10q25.1 P28, SPG-R, GSTO 1-1, GSTTLp28, HEL-S-21 -GSTO1 and Bladder Cancer
4
MALAT1 11q13.1 HCN, NEAT2, PRO2853, mascRNA, LINC00047, NCRNA00047 -MALAT1 and Bladder Cancer
4
POLB 8p11.2 -POLB and Bladder Cancer
4
GSTM3 1p13.3 GST5, GSTB, GTM3, GSTM3-3 -GSTM3 and Bladder Cancer
4
CCR5 3p21.31 CKR5, CCR-5, CD195, CKR-5, CCCKR5, CMKBR5, IDDM22, CC-CKR-5 -CCR5 and Bladder Cancer
4
S100A9 1q21 MIF, NIF, P14, CAGB, CFAG, CGLB, L1AG, LIAG, MRP14, 60B8AG, MAC387 -S100A9 and Bladder Cancer
4
EWSR1 22q12.2 EWS, bK984G1.4 -EWSR1 and Bladder Cancer
4
MMP3 11q22.3 SL-1, STMY, STR1, CHDS6, MMP-3, STMY1 -MMP3 and Bladder Cancer
4
PIK3R1 5q13.1 p85, AGM7, GRB1, IMD36, p85-ALPHA -PIK3R1 and Bladder Cancer
4
LRIG1 3p14 LIG1, LIG-1 -LRIG1 and Bladder Cancer
4
HGF 7q21.1 SF, HGFB, HPTA, F-TCF, DFNB39 -HGF and Bladder Cancer
4
MIR10A 17q21.32 MIRN10A, mir-10a, miRNA10A, hsa-mir-10a -miR-10a and Bladder Cancer
4
MAPK3 16p11.2 ERK1, ERT2, ERK-1, PRKM3, P44ERK1, P44MAPK, HS44KDAP, HUMKER1A, p44-ERK1, p44-MAPK -MAPK3 and Bladder Cancer
4
LGALS1 22q13.1 GBP, GAL1 -LGALS1 and Bladder Cancer
4
FGF1 5q31 AFGF, ECGF, FGFA, ECGFA, ECGFB, FGF-1, HBGF1, HBGF-1, GLIO703, ECGF-beta, FGF-alpha -FGF1 and Bladder Cancer
4
FLT1 13q12 FLT, FLT-1, VEGFR1, VEGFR-1 -FLT1 Expression in Bladder Cancer
4
COMT 22q11.21 HEL-S-98n -COMT and Bladder Cancer
4
FSCN1 7p22 HSN, SNL, p55, FAN1 -FSCN1 and Bladder Cancer
3
MTRR 5p15.31 MSR, cblE -MTRR and Bladder Cancer
3
S100A8 1q21 P8, MIF, NIF, CAGA, CFAG, CGLA, L1Ag, MRP8, CP-10, MA387, 60B8AG -S100A8 and Bladder Cancer
3
NOX1 Xq22 MOX1, NOH1, NOH-1, GP91-2 -NOX1 and Bladder Cancer
3
CDK1 10q21.1 CDC2, CDC28A, P34CDC2 -CDK1 and Bladder Cancer
3
MUC7 4q13.3 MG2 -MUC7 and Bladder Cancer
3
CKS2 9q22 CKSHS2 -CKS2 and Bladder Cancer
3
XRCC5 2q35 KU80, KUB2, Ku86, NFIV, KARP1, KARP-1 -XRCC5 and Bladder Cancer
3
HDAC4 2q37.3 HD4, AHO3, BDMR, HDACA, HA6116, HDAC-4, HDAC-A -HDAC4 and Bladder Cancer
3
GSTO2 10q25.1 GSTO 2-2, bA127L20.1 -GSTO2 and Bladder Cancer
3
COL18A1 21q22.3 KS, KNO, KNO1 -COL18A1 and Bladder Cancer
3
UGT2B7 4q13 UGT2B9, UDPGTH2, UDPGT2B7, UDPGT 2B9 -UGT2B7 and Bladder Cancer
3
MGEA5 10q24.1-q24.3 OGA, MEA5, NCOAT -MGEA5 and Bladder Cancer
3
MAP2K6 17q24.3 MEK6, MKK6, MAPKK6, PRKMK6, SAPKK3, SAPKK-3 -MAP2K6 and Bladder Cancer
3
ACTB 7p22 BRWS1, PS1TP5BP1 -ACTB and Bladder Cancer
3
RAF1 3p25 NS5, CRAF, Raf-1, c-Raf, CMD1NN -RAF1 and Bladder Cancer
3
SFRP2 4q31.3 FRP-2, SARP1, SDF-5 -SFRP2 and Bladder Cancer
3
IGFBP5 2q35 IBP5 -IGFBP5 and Bladder Cancer
3
DICER1 14q32.13 DCR1, MNG1, Dicer, HERNA, RMSE2, Dicer1e, K12H4.8-LIKE -DICER1 and Bladder Cancer
3
PDGFRB 5q33.1 IMF1, IBGC4, JTK12, PDGFR, CD140B, PDGFR1, PDGFR-1 -PDGFRB and Bladder Cancer
3
CD47 3q13.1-q13.2 IAP, OA3, MER6 -CD47 and Bladder Cancer
3
MMP14 14q11.2 MMP-14, MMP-X1, MT-MMP, MT1MMP, MTMMP1, WNCHRS, MT1-MMP, MT-MMP 1 -MMP14 and Bladder Cancer
3
STAR 8p11.2 STARD1 -STAR and Bladder Cancer
3
RHOA 3p21.3 ARHA, ARH12, RHO12, RHOH12 -RHOA and Bladder Cancer
3
TP73 1p36.3 P73 -TP73 Overexpression in Bladder Cancer
3
NOS3 7q36 eNOS, ECNOS -NOS3 and Bladder Cancer
3
LAMC2 1q25-q31 B2T, CSF, EBR2, BM600, EBR2A, LAMB2T, LAMNB2 -LAMC2 and Bladder Cancer
3
MAGEA1 Xq28 CT1.1, MAGE1 -MAGEA1 and Bladder Cancer
3
FGF4 11q13.3 HST, KFGF, HST-1, HSTF1, K-FGF, HBGF-4 -FGF4 and Bladder Cancer
3
CCNA1 13q12.3-q13 CT146 -CCNA1 and Bladder Cancer
3
DEK 6p22.3 D6S231E -DEK and Bladder Cancer
3
VHL 3p25.3 RCA1, VHL1, pVHL, HRCA1 -VHL and Bladder Cancer
3
CALCA 11p15.2 CT, KC, CGRP, CALC1, CGRP1, CGRP-I -CALCA and Bladder Cancer
2
NCOA1 2p23 SRC1, KAT13A, RIP160, F-SRC-1, bHLHe42, bHLHe74 -NCOA1 and Bladder Cancer
2
CDKN2D 19p13 p19, INK4D, p19-INK4D -CDKN2D and Bladder Cancer
2
BCHE 3q26.1-q26.2 E1, CHE1, CHE2 -BCHE and Bladder Cancer
2
S100P 4p16 MIG9 -S100P and Bladder Cancer
2
SDC4 20q12 SYND4 -SDC4 and Bladder Cancer
2
IMP3 15q24 BRMS2, MRPS4, C15orf12 -IMP3 and Bladder Cancer
2
FEZ1 11q24.2 -FEZ1 and Bladder Cancer
2
SMAD2 18q21.1 JV18, MADH2, MADR2, JV18-1, hMAD-2, hSMAD2 -SMAD2 and Bladder Cancer
2
MCM5 22q13.1 CDC46, P1-CDC46 -MCM5 and Bladder Cancer
2
ANXA1 9q21.13 ANX1, LPC1 -ANXA1 and Bladder Cancer
2
DAB2IP 9q33.1-q33.3 AIP1, AIP-1, AF9Q34, DIP1/2 -DAB2IP and Bladder Cancer
2
HAS3 16q22.1 -HAS3 and Bladder Cancer
2
PCDH10 4q28.3 PCDH19, OL-PCDH -PCDH10 and Bladder Cancer
2
MAP2K4 17p12 JNKK, MEK4, MKK4, SEK1, SKK1, JNKK1, SERK1, MAPKK4, PRKMK4, SAPKK1, SAPKK-1 -MAP2K4 and Bladder Cancer
2
MMP12 11q22.3 ME, HME, MME, MMP-12 -MMP12 and Bladder Cancer
2
GLI2 2q14 CJS, HPE9, PHS2, THP1, THP2 -GLI2 and Bladder Cancer
2
GLI3 7p13 PHS, ACLS, GCPS, PAPA, PAPB, PAP-A, PAPA1, PPDIV, GLI3FL, GLI3-190 -GLI3 and Bladder Cancer
2
TAGLN 11q23.2 SM22, SMCC, TAGLN1, WS3-10 -TAGLN and Bladder Cancer
2
NQO2 6p25.2 QR2, DHQV, DIA6, NMOR2 -NQO2 and Bladder Cancer
2
KISS1R 19p13.3 HH8, CPPB1, GPR54, AXOR12, KISS-1R, HOT7T175 -KISS1R and Bladder Cancer
2
WWOX 16q23 FOR, WOX1, EIEE28, FRA16D, SCAR12, HHCMA56, PRO0128, SDR41C1, D16S432E -WWOX and Bladder Cancer
2
RHEB 7q36 RHEB2 -RHEB and Bladder Cancer
2
HOXD10 2q31.1 HOX4, HOX4D, HOX4E, Hox-4.4 -HOXD10 and Bladder Cancer
2
UBE2C 20q13.12 UBCH10, dJ447F3.2 -UBE2C and Bladder Cancer
2
CTAG1B Xq28 CTAG, ESO1, CT6.1, CTAG1, LAGE-2, LAGE2B, NY-ESO-1 -CTAG1B and Bladder Cancer
2
MMP8 11q22.3 HNC, CLG1, MMP-8, PMNL-CL -MMP8 and Bladder Cancer
2
ITGB4 17q25 CD104 -ITGB4 and Bladder Cancer
2
SPINK1 5q32 TCP, PCTT, PSTI, TATI, Spink3 -SPINK1 and Bladder Cancer
2
HYAL1 3p21.31 MPS9, NAT6, LUCA1, HYAL-1 -HYAL1 and Bladder Cancer
2
RALB 2q14.2 -RALB and Bladder Cancer
2
RREB1 6p25 HNT, FINB, LZ321, Zep-1, RREB-1 -RREB1 and Bladder Cancer
2
IL4 5q31.1 BSF1, IL-4, BCGF1, BSF-1, BCGF-1 -IL4 and Bladder Cancer
2
KLF5 13q22.1 CKLF, IKLF, BTEB2 -KLF5 and Bladder Cancer
2
BUB1 2q14 BUB1A, BUB1L, hBUB1 -BUB1 and Bladder Cancer
2
TNFSF15 9q32 TL1, TL1A, VEGI, VEGI192A -TNFSF15 expression in Bladder Cancer
2
PLAT 8p12 TPA, T-PA -PLAT and Bladder Cancer
2
NOX4 11q14.2-q21 KOX, KOX-1, RENOX -NOX4 and Bladder Cancer
2
ITGB3 17q21.32 GT, CD61, GP3A, BDPLT2, GPIIIa, BDPLT16 -ITGB3 and Bladder Cancer
2
MAD2L1 4q27 MAD2, HSMAD2 -MAD2L1 and Bladder Cancer
2
ERCC4 16p13.12 XPF, RAD1, FANCQ, ERCC11 -ERCC4 and Bladder Cancer
2
MCM2 3q21 BM28, CCNL1, CDCL1, cdc19, D3S3194, MITOTIN -MCM2 and Bladder Cancer
2
MBD2 18q21 DMTase, NY-CO-41 -MBD2 and Bladder Cancer
2
RAD23B 9q31.2 P58, HR23B, HHR23B -RAD23B and Bladder Cancer
2
CEACAM1 19q13.2 BGP, BGP1, BGPI -CEACAM1 and Bladder Cancer
2
CUL3 2q36.2 CUL-3, PHA2E -CUL3 and Bladder Cancer
2
RHOBTB2 8p21.3 DBC2 -RHOBTB2 and Bladder Cancer
2
IL12A 3q25.33 P35, CLMF, NFSK, NKSF1, IL-12A -IL12A and Bladder Cancer
1
IL17C 16q24 CX2, IL-17C -IL17C and Bladder Cancer
1
ATP7B 13q14.3 WD, PWD, WC1, WND -ATP7B and Bladder Cancer
1
ARF1 1q42 -ARF1 and Bladder Cancer
1
RIN1 11q13.2 -RIN1 and Bladder Cancer
1
LASP1 17q11-q21.3 MLN50, Lasp-1 -LASP1 and Bladder Cancer
1
ENDOU 12q13.1 P11, PP11, PRSS26 -ENDOU and Bladder Cancer
1
TRAF6 11p12 RNF85, MGC:3310 -TRAF6 and Bladder Cancer
1
ESPL1 12q ESP1, SEPA GWS
-ESPL1 and Bladder Cancer
1
TNFRSF25 1p36.2 DR3, TR3, DDR3, LARD, APO-3, TRAMP, WSL-1, WSL-LR, TNFRSF12 -TNFRSF25 and Bladder Cancer
1
YWHAZ 8q23.1 HEL4, YWHAD, KCIP-1, HEL-S-3, 14-3-3-zeta -YWHAZ and Bladder Cancer
1
BMPR2 2q33-q34 BMR2, PPH1, BMPR3, BRK-3, POVD1, T-ALK, BMPR-II -BMPR2 and Bladder Cancer
1
WHSC1L1 8p11.2 NSD3, pp14328 -WHSC1L1 and Bladder Cancer
1
TBX2 17q23.2 -TBX2 and Bladder Cancer
1
AIM1 6q21 ST4, CRYBG1 -AIM1 and Bladder Cancer
1
BCL2L12 19q13.3 -BCL2L12 and Bladder Cancer
1
HLA-G 6p21.3 MHC-G -HLA-G and Bladder Cancer
1
PRC1 15q26.1 ASE1 -PRC1 and Bladder Cancer
1
FH 1q42.1 MCL, FMRD, LRCC, HLRCC, MCUL1 -FH and Bladder Cancer
1
EEF1E1 6p24.3 P18, AIMP3 -EEF1E1 and Bladder Cancer
1
ANO1 11q13.3 DOG1, TAOS2, ORAOV2, TMEM16A -ANO1 and Bladder Cancer
1
RCVRN 17p13.1 RCV1 -RCVRN and Bladder Cancer
1
SMARCA2 9p22.3 BRM, SNF2, SWI2, hBRM, NCBRS, Sth1p, BAF190, SNF2L2, SNF2LA, hSNF2a -SMARCA2 and Bladder Cancer
1
HDAC6 Xp11.23 HD6, JM21, CPBHM, PPP1R90 -HDAC6 and Bladder Cancer
1
EML4 2p21 C2orf2, ELP120, EMAP-4, EMAPL4, ROPP120 -EML4 and Bladder Cancer
1
DRD2 11q23 D2R, D2DR -DRD2 and Bladder Cancer
1
NRG1 8p12 GGF, HGL, HRG, NDF, ARIA, GGF2, HRG1, HRGA, SMDF, MST131, MSTP131, NRG1-IT2 -NRG1 and Bladder Cancer
1
ADH1C 4q23 ADH3 -ADH1C and Bladder Cancer
1
TYK2 19p13.2 JTK1, IMD35 -TYK2 and Bladder Cancer
1
TNKS 8p23.1 TIN1, ARTD5, PARPL, TINF1, TNKS1, pART5, PARP5A, PARP-5a -TNKS and Bladder Cancer
1
TPTE 21p11 CT44, PTEN2 -TPTE and Bladder Cancer
1
GNL3 3p21.1 NS, E2IG3, NNP47, C77032 -GNL3 and Bladder Cancer
1
MSI1 12q24 -MSI1 and Bladder Cancer
1
S100B 21q22.3 NEF, S100, S100-B, S100beta -S100B and Bladder Cancer
1
HLA-E 6p21.3 MHC, QA1, EA1.2, EA2.1, HLA-6.2 -HLA-E and Bladder Cancer
1
MEG3 14q32 GTL2, FP504, prebp1, PRO0518, PRO2160, LINC00023, NCRNA00023 -MEG3 and Bladder Cancer
1
WRN 8p12 RECQ3, RECQL2, RECQL3 -WRN and Bladder Cancer
1
CASP2 7q34-q35 ICH1, NEDD2, CASP-2, NEDD-2, PPP1R57 -CASP2 and Bladder Cancer
1
RRM1 11p15.5 R1, RR1, RIR1 -RRM1 and Bladder Cancer
1
LINC00632 Xq27.1 -RP1-177G6.2 and Bladder Cancer
1
IRAK1 Xq28 IRAK, pelle -IRAK1 and Bladder Cancer
1
ACVRL1 12q13.13 HHT, ALK1, HHT2, ORW2, SKR3, ALK-1, TSR-I, ACVRLK1 -ACVRL1 and Bladder Cancer
1
FGF7 15q21.2 KGF, HBGF-7 -FGF7 and Bladder Cancer
1
NUMB 14q24.3 S171, C14orf41, c14_5527 -NUMB and Bladder Cancer
1
PLK2 5q12.1-q13.2 SNK, hSNK, hPlk2 -PLK2 and Bladder Cancer
1
EPHB4 7q22 HTK, MYK1, TYRO11 -EPHB4 and Bladder Cancer
1
NONO Xq13.1 P54, NMT55, NRB54, P54NRB, PPP1R114 -NONO and Bladder Cancer
1
HSD3B2 1p13.1 HSDB, HSD3B, SDR11E2 -HSD3B2 and Bladder Cancer
1
S100A1 1q21 S100, S100A, S100-alpha -S100A1 and Bladder Cancer
1
PDCD6 5p15.33 ALG2, ALG-2, PEF1B -PDCD6 and Bladder Cancer
1
KAT5 11q13 TIP, ESA1, PLIP, TIP60, cPLA2, HTATIP, ZC2HC5, HTATIP1 -KAT5 and Bladder Cancer
1
TACSTD2 1p32 EGP1, GP50, M1S1, EGP-1, TROP2, GA7331, GA733-1 -TACSTD2 and Bladder Cancer
1
IRF7 11p15.5 IRF7A, IRF7B, IRF7C, IRF7H, IRF-7H -IRF7 and Bladder Cancer
1
IRF9 14q11.2 p48, IRF-9, ISGF3, ISGF3G -IRF9 and Bladder Cancer
1
FGFR4 5q35.2 TKF, JTK2, CD334 -FGFR4 and Bladder Cancer
1
AMFR 16q21 GP78, RNF45 -AMFR and Bladder Cancer
1
MSI2 17q22 MSI2H -MSI2 and Bladder Cancer
1
DGCR8 22q11.2 Gy1, pasha, DGCRK6, C22orf12 -DGCR8 and Bladder Cancer
1
ELN 7q11.23 WS, WBS, SVAS -ELN and Bladder Cancer
1
GRASP 12q13.13 TAMALIN -GRASP and Bladder Cancer
1
MUC5B 11p15.5 MG1, MUC5, MUC9, MUC-5B -MUC5B and Bladder Cancer
1
CASP5 11q22.2-q22.3 ICH-3, ICEREL-III, ICE(rel)III -CASP5 and Bladder Cancer
1
OPCML 11q25 OPCM, OBCAM, IGLON1 -OPCML and Bladder Cancer
1
PSIP1 9p22.3 p52, p75, PAIP, DFS70, LEDGF, PSIP2 -PSIP1 and Bladder Cancer
1
AIFM1 Xq26.1 AIF, CMT2D, CMTX4, COWCK, NADMR, NAMSD, PDCD8, COXPD6 -AIFM1 and Bladder Cancer
1
FABP5 8q21.13 EFABP, KFABP, E-FABP, PAFABP, PA-FABP -FABP5 and Bladder Cancer
1
CEBPB 20q13.1 TCF5, IL6DBP, NF-IL6, C/EBP-beta -CEBPB and Bladder Cancer
1
SLC7A5 16q24.3 E16, CD98, LAT1, 4F2LC, MPE16, hLAT1, D16S469E -SLC7A5 and Bladder Cancer
1
CSF3R 1p35-p34.3 CD114, GCSFR -CSF3R and Bladder Cancer
1
TBX3 12q24.21 UMS, XHL, TBX3-ISO -TBX3 and Bladder Cancer
1
NUMA1 11q13 NUMA, NMP-22 -NUMA1 and Bladder Cancer
1
CYP2A13 19q13.2 CPAD, CYP2A, CYPIIA13 -CYP2A13 and Bladder Cancer
1
FGF19 11q13.1 -FGF19 and Bladder Cancer
1
DLEC1 3p21.3 F56, DLC1, CFAP81 -DLEC1 and Bladder Cancer
1
SRPX Xp21.1 DRS, ETX1, SRPX1, HEL-S-83p -SRPX and Bladder Cancer
1
UGT2B17 4q13 BMND12, UDPGT2B17 -UGT2B17 and Bladder Cancer
1
SHMT1 17p11.2 SHMT, CSHMT -SHMT1 and Bladder Cancer
1
CHRNB4 15q24 -CHRNB4 and Bladder Cancer
1
NRP2 2q33.3 NP2, NPN2, PRO2714, VEGF165R2 -NRP2 and Bladder Cancer
1
MAD1L1 7p22 MAD1, PIG9, TP53I9, TXBP181 -MAD1L1 and Bladder Cancer
1
KLK5 19q13.33 SCTE, KLKL2, KLK-L2 -KLK5 and Bladder Cancer
1
S100A3 1q21 S100E -S100A3 and Bladder Cancer
1
IL4R 16p12.1-p11.2 CD124, IL4RA, IL-4RA -IL4R and Bladder Cancer
1
CBX7 22q13.1 -CBX7 and Bladder Cancer
1
KLK6 19q13.3 hK6, Bssp, Klk7, SP59, PRSS9, PRSS18 -KLK6 and Bladder Cancer
1
LHCGR 2p21 HHG, LHR, LCGR, LGR2, ULG5, LHRHR, LSH-R, LH/CGR, LH/CG-R -LHCGR and Bladder Cancer
1
PNN 14q21.1 DRS, DRSP, SDK3, memA -PNN and Bladder Cancer
1
GNAS 20q13.3 AHO, GSA, GSP, POH, GPSA, NESP, GNAS1, PHP1A, PHP1B, PHP1C, C20orf45 -GNAS and Bladder Cancer
1
RASAL1 12q23-q24 RASAL -RASAL1 and Bladder Cancer
1
LAMB3 1q32 AI1A, LAM5, LAMNB1, BM600-125KDA -LAMB3 and Bladder Cancer
1
ITGA4 2q31.3 IA4, CD49D -ITGA4 and Bladder Cancer
1
MCM4 8q11.2 NKCD, CDC21, CDC54, NKGCD, hCdc21, P1-CDC21 -MCM4 and Bladder Cancer
1
IL17A 6p12 IL17, CTLA8, IL-17, IL-17A -IL17A and Bladder Cancer
1
MTSS1 8p22 MIM, MIMA, MIMB -MTSS1 and Bladder Cancer
1
GATA2 3q21.3 DCML, IMD21, NFE1B, MONOMAC -GATA2 and Bladder Cancer
1
XRCC6 22q13.2 ML8, KU70, TLAA, CTC75, CTCBF, G22P1 -XRCC6 and Bladder Cancer
1
SMPD1 11p15.4-p15.1 ASM, NPD, ASMASE -SMPD1 and Bladder Cancer
1
LRIG3 12q14.1 LIG3 -LRIG3 and Bladder Cancer
1
ITGA6 2q31.1 CD49f, VLA-6, ITGA6B -ITGA6 and Bladder Cancer
1
LDLR 19p13.2 FH, FHC, LDLCQ2 -LDLR and Bladder Cancer
1
MYCL 1p34.2 LMYC, L-Myc, MYCL1, bHLHe38 -MYCL and Bladder Cancer
1
IL12B 5q33.3 CLMF, NKSF, CLMF2, IMD28, IMD29, NKSF2, IL-12B -IL12B and Bladder Cancer
1
HTRA1 10q26.3 L56, HtrA, ARMD7, ORF480, PRSS11, CARASIL -HTRA1 and Bladder Cancer
1
LTB 6p21.3 p33, TNFC, TNFSF3 -LTB and Bladder Cancer
1
AGTR2 Xq22-q23 AT2, ATGR2, MRX88 -AGTR2 and Bladder Cancer
1
MYOD1 11p15.4 PUM, MYF3, MYOD, bHLHc1 -MYOD1 and Bladder Cancer
1
TANK 2q24.2 ITRAF, TRAF2, I-TRAF -TANK and Bladder Cancer
1
S100A7 1q21 PSOR1, S100A7c -S100A7 and Bladder Cancer
1
CXCL11 4q21.2 IP9, H174, IP-9, b-R1, I-TAC, SCYB11, SCYB9B -CXCL11 and Bladder Cancer
1
BUB3 10q26 BUB3L, hBUB3 -BUB3 and Bladder Cancer
1
CAV2 7q31.1 CAV -CAV2 and Bladder Cancer
1
NEFL 8p21 NFL, NF-L, NF68, CMT1F, CMT2E, PPP1R110 -NEFL and Bladder Cancer
1
PPP1R13L 19q13.32 RAI, RAI4, IASPP, NKIP1 -PPP1R13L and Bladder Cancer
1
HOXA13 7p15.2 HOX1, HOX1J -HOXA13 and Bladder Cancer
1
FLNA Xq28 FLN, FMD, MNS, OPD, ABPX, CSBS, CVD1, FLN1, NHBP, OPD1, OPD2, XLVD, XMVD, FLN-A, ABP-280 -FLNA and Bladder Cancer
1
ALOX5 10q11.2 5-LO, 5LPG, LOG5, 5-LOX -ALOX5 and Bladder Cancer
1
ATIC 2q35 PURH, AICAR, AICARFT, IMPCHASE, HEL-S-70p -ATIC and Bladder Cancer
1
SMARCA4 19p13.2 BRG1, SNF2, SWI2, MRD16, RTPS2, BAF190, SNF2L4, SNF2LB, hSNF2b, BAF190A -SMARCA4 and Bladder Cancer
1
KIAA1524 3q13.13 p90, CIP2A -KIAA1524 and Bladder Cancer
1
BAI1 8q24.3 GDAIF -BAI1 and Bladder Cancer
1

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications

El-Gamal EM, Gouida MS
Flow cytometric study of cell cycle and DNA ploidy in bilharzial bladder cancer.
Clin Lab. 2015; 61(3-4):211-8 [PubMed] Related Publications
BACKGROUND: Tumor grade and stage are currently the most important prognostic variables in bladder cancer but establishing additional criteria is still needed for effective treatment. In this study, we analyzed DNA ploidy and the cell cycle: gap one stage (GO/1), synthesis stage (S-phase%), and gap two stage (G2/M) in urine and blood cells of bilharzial bladder cancer patients.
METHODS: The cell cycle and DNA ploidy were investigated using a flow cytometric technique for 150 bilharzial bladder cancer patients and 60 healthy normal controls.
RESULTS: This study demonstrated that GO/1 levels were significantly decreased in urine and blood cells of bladder cancer patients compared to controls and these decreases were significant in urine cells compared to blood cells and at high grade and stage. In contrast, S-phase%, G2/M, coefficient variation (CV), and DNA index (DI) levels were increased in urine and blood cells of patients compared to those of controls. These levels were significantly increased in urine patients compared to their blood. Finally, the undetectable DNA aneuploidy in control cells was significantly increased in urine cells of patients compared to their blood cells at higher grade and stage.
CONCLUSIONS: Taken together, the cell cycle and DNA aneuploidy analysis especially in urine cells of bilharzial bladder cancer patients may help in diagnosis, prognosis, and clinical treatment and can be considered as an additional marker for bladder cancer.

Mitra AP, Lerner SP
Potential role for targeted therapy in muscle-invasive bladder cancer: lessons from the cancer genome atlas and beyond.
Urol Clin North Am. 2015; 42(2):201-15, viii [PubMed] Related Publications
The Cancer Genome Atlas project has identified and confirmed several important molecular alterations that form the basis for tumorigenesis and disease progression in muscle-invasive bladder cancer. Profiling studies also have reported on validated biomarker panels that predict prognosis and may be used to identify patients who require more aggressive therapy. This article describes the major molecular alterations in muscle-invasive urothelial carcinoma, and how several of these are being investigated as targets for novel therapeutics. It also highlights studies that identify biomarkers for platinum sensitivity, and efforts to integrate targeted therapeutics and companion theranostics for personalized treatment of muscle-invasive bladder cancer.

Cheah MT, Chen JY, Sahoo D, et al.
CD14-expressing cancer cells establish the inflammatory and proliferative tumor microenvironment in bladder cancer.
Proc Natl Acad Sci U S A. 2015; 112(15):4725-30 [PubMed] Free Access to Full Article Related Publications
Nonresolving chronic inflammation at the neoplastic site is consistently associated with promoting tumor progression and poor patient outcomes. However, many aspects behind the mechanisms that establish this tumor-promoting inflammatory microenvironment remain undefined. Using bladder cancer (BC) as a model, we found that CD14-high cancer cells express higher levels of numerous inflammation mediators and form larger tumors compared with CD14-low cells. CD14 antigen is a glycosyl-phosphatidylinositol (GPI)-linked glycoprotein and has been shown to be critically important in the signaling pathways of Toll-like receptor (TLR). CD14 expression in this BC subpopulation of cancer cells is required for increased cytokine production and increased tumor growth. Furthermore, tumors formed by CD14-high cells are more highly vascularized with higher myeloid cell infiltration. Inflammatory factors produced by CD14-high BC cells recruit and polarize monocytes and macrophages to acquire immune-suppressive characteristics. In contrast, CD14-low BC cells have a higher baseline cell division rate than CD14-high cells. Importantly, CD14-high cells produce factors that further increase the proliferation of CD14-low cells. Collectively, we demonstrate that CD14-high BC cells may orchestrate tumor-promoting inflammation and drive tumor cell proliferation to promote tumor growth.

Antonova O, Yossifova L, Staneva R, et al.
Changes in the gene expression profile of the bladder cancer cell lines after treatment with Helix lucorum and Rapana venosa hemocyanin.
J BUON. 2015 Jan-Feb; 20(1):180-7 [PubMed] Related Publications
PURPOSE: The purpose of this study was to elucidate the mechanism of action of the Helix lucorum hemocyanin (HlH), b-HlH-h, and RvH2-g hemocyanins as potential agents against bladder cancer.
METHODS: We evaluated the viability of 647-V, T-24, and CAL-29 bladder cancer cell lines after treatment with the tested hemocyanins. The cell viability was measured at 72 hrs with MTT and WST-1 assays. Acridine orange/propidium iodide double staining was used to discriminate between apoptotic and necrotic cells. Gene expression profiling of the 168 genes from human inflammatory cytokines and signal transduction pathways were performed on the tumor cells before and after hemocyanins' treatment.
RESULTS: The results showed decreased survival of cancer cells in the presence of HlH and two functional units: b-HlH-h and RvH2-g. Acridine orange/propidium iodide double staining revealed that the decreased viability was due to apoptosis. The gene expression data showed upregulation of genes involved in the apoptosis as well as of the immune system activation, and downregulation of the CCL2, CCL17, CCL21, CXCL1, and ABCF1 genes.
CONCLUSIONS: The present study is the first to report gene expression in human cells under the influence of hemocyanins. The mechanism of antitumor activity of the HlH, b-HlH-h, and RvH2-g hemocyanins includes induction of apoptosis. In addition to the antiproliferative effect, downregulation of the genes with metastatic potential was observed. Together with the already known immunogenic effect, these findings support further studies on hemocyanins as potential therapeutic agents against bladder cancer.

Borah S, Xi L, Zaug AJ, et al.
Cancer. TERT promoter mutations and telomerase reactivation in urothelial cancer.
Science. 2015; 347(6225):1006-10 [PubMed] Related Publications
Reactivation of telomerase, the chromosome end-replicating enzyme, drives human cell immortality and cancer. Point mutations in the telomerase reverse transcriptase (TERT) gene promoter occur at high frequency in multiple cancers, including urothelial cancer (UC), but their effect on telomerase function has been unclear. In a study of 23 human UC cell lines, we show that these promoter mutations correlate with higher levels of TERT messenger RNA (mRNA), TERT protein, telomerase enzymatic activity, and telomere length. Although previous studies found no relation between TERT promoter mutations and UC patient outcome, we find that elevated TERT mRNA expression strongly correlates with reduced disease-specific survival in two independent UC patient cohorts (n = 35; n = 87). These results suggest that high telomerase activity may be a better marker of aggressive UC tumors than TERT promoter mutations alone.

Li W, Kidiyoor A, Hu Y, et al.
Evaluation of transforming growth factor-β1 suppress Pokemon/epithelial-mesenchymal transition expression in human bladder cancer cells.
Tumour Biol. 2015; 36(2):1155-62 [PubMed] Related Publications
Transforming growth factor-β1 (TGF-β1) plays a dual role in apoptosis and in proapoptotic responses in the support of survival in a variety of cells. The aim of this study was to determine the function of TGF-β1 in bladder cancer cells and the relationship with POK erythroid myeloid ontogenic factor (Pokemon). TGF-β1 and its receptors mediate several tumorigenic cascades that regulate cell proliferation, migration, and survival of bladder cancer cells. Bladder cancer cells T24 were treated with different levels of TGF-β1. Levels of Pokemon, E-cadherin, Snail, MMP2, MMP9, Twist, VEGF, and β-catenin messenger RNA (mRNA) and protein were examined by real-time quantitative fluorescent PCR and Western blot analysis, respectively. The effects of TGF-β1 on epithelial-mesenchymal transition of T24 cells were evaluated with wound-healing assay, proliferation of T24 was evaluated with reference to growth curves with MTT assay, and cell invasive ability was investigated by Transwell assay. Data show that Pokemon was inhibited by TGF-β1 treatment; the gene and protein of E-cadherin and β-catenin expression level showed decreased markedly after TGF-β1 treatment (P < 0.05). While the bladder cancer cell after TGF-β1 treatment showed a significantly reduced wound-closing efficiency at 6, 12, and 24 h, mechanistic analyses demonstrated that different levels of TGF-β1 promotes tumor cell growth, migration, and invasion in bladder cancer cells (P < 0.01, P < 0.05, respectively). In summary, our findings suggest that TGF-β1 may inhibit the expression of Pokemon, β-catenin, and E-cadherin. The high expression of TGF-β1 leads to an increase in the phenotype and apical-base polarity of epithelial cells. These changes of cells may result in the recurrence and progression of bladder cancer at last. Related mechanism is worthy of further investigation.

Akhmadishina LZ, Giliazova IR, Kutlyeva LR, et al.
[DNA repair XRCC1, XPD genes polymorphism as associated with the development of bladder cancer and renal cell carcinoma].
Genetika. 2014; 50(4):481-90 [PubMed] Related Publications
We examined the correlations between the polymorphic alleles of the DNA repair genes XRCC1 (c.839G> A, rs25489; and c.1196A> G, rs25487), XPA (c.-4A> G, rs1800975), and XPD (c.2251A> C, rs13181) and the progression and severity of neoplasias in the bladder and kidney in patients of three distinct ethnic groups, Bashkir, Russians, and Tatar, residing in the Republic of Bashkorostan. The study enrolled 468 cancer patients and 351 healthy individuals. Genotyping for polymorphic alleles was carried out using the PCR-RFLP method. We identified a correlation between allele A of the c.839 G>A locus of the XRCC1 gene and the incidence of the bladder cancer (BC) and kidney cancer (KC) in the Tatar study group, using the additive genetic effects model (Odds Ratio (OR) = 5.23 and OR = 3.90). In turn, the heterozygous G/A genotype was present at a significantly higher frequency in the KC patients of Bashkir ethnic origin, compared with the control group (p = 0.0061, OR= 4.72). Additional analysis with consideration of participants' smoking status showed that the G/A genotype is significantly more frequent in smokers with BC (OR = 1.96, p = 0.05) then in healthy smokers. We also determined, using the recessive genetic model, that the genotype A/A of the c. 1196A>G locus of the XRCC1 gene was correlated with a higher risk of BC in the Russian cohort (OR = 2.29, p = 0.0082) and an increased incidence of KC in the Bashkir group (OR = 4.06, p = 0.05). A similar correlation was obtained for smokers. In contrast, the allele c.2251 A>C in the XPD gene correlated with a lower risk for BC and KC in the Tatars (p = 0.0003, OR = 0.48 and p < 0.0001, OR = 0.37) in the additive model and in the Bashkirs (p = 0.0083, OR = 0.12) and Russians (p = 0.0001, OR = 0.14) in the recessive model. Further, we uncovered that polymorphism c.839 G>A in the XRCC1 gene contributes to the progression of noninvasive and invasive BC and promotes KC at early and advanced stages of the disease. Thus, we identified similar correlations between DNA repair gene polymorphism and the incidence and progression of BC and KC. We propose that this result points to the involvement of common pathogenetic mechanisms in the initiation and progression of the urinary neoplasias.

Jia Z, Ai X, Sun F, et al.
Identification of new hub genes associated with bladder carcinoma via bioinformatics analysis.
Tumori. 2015 Jan-Feb; 101(1):117-22 [PubMed] Related Publications
AIMS AND BACKGROUND: Bladder carcinoma (BC) is one of the most common malignant cancers worldwide. Several genes related to the mechanism of BC have been studied in recent years, but the current understanding of BC is still rather limited. This study aimed to find new differentially expressed genes (DEGs) associated with the occurrence and development of BC.
METHODS: In this work, we downloaded gene expression data from Gene Expression Omnibus under accession number GSE27448, which included 10 GeneChips from urinary BC tissues and 5 from normal tissues. DEGs were identified by the LIMMA package in R. Then the protein-protein interactions (PPIs) networks were analyzed with the database of Search Tool for the Retrieval of Interacting Genes, and gene ontology (GO) was applied to explore the underlying function of the DEGs using the Database for Annotation, Visualization and Integrated Discovery.
RESULTS: A total of 2,068 DEGs were found between BC and normal tissues. These genes were involved in 49 functional clusters. The top 10 highest degree nodes, such as POLR2F/2H (DNA directed RNA polymerase II polypeptide F/polypeptide H) and RPS14/15 (ribosomal protein S14/S15), were proven to be hub nodes in the PPIs network. ITGA7 (integrin, alpha 7), GRB14 (growth factor receptor-bound protein 14), CDC20 (cell division cycle 20) and PSMB1 (proteasome subunit, beta type, 1) were significant DEGs identified in the functional clusters.
CONCLUSIONS: Genes such as POLR2F/2H, RPS14/15, ITGA7, GRB14, CDC20 and PSMB1 were forecast to play important roles in the occurrence and progression of BC.

Wang K, Liu T, Liu C, et al.
TERT promoter mutations and TERT mRNA but not FGFR3 mutations are urinary biomarkers in Han Chinese patients with urothelial bladder cancer.
Oncologist. 2015; 20(3):263-9 [PubMed] Article available free on PMC after 01/03/2016 Related Publications
The TERT promoter and FGFR3 gene mutations are two of the most common genetic events in urothelial bladder cancer (UBC), and these mutation assays in patient urine have been shown to be promising biomarkers for UBC diagnosis and surveillance. These results were obtained mainly from studies of patients with UBC in Western countries, and little is known about such information in Han Chinese patients with UBC. In the present study, we addressed this issue by analyzing tumors from 182 Han Chinese patients with UBC and urine samples from 102 patients for mutations in the TERT promoter and FGFR3 and TERT mRNA expression in tumors and/or urine. TERT promoter and FGFR3 mutations were identified in 87 of 182 (47.8%) and 7 of 102 (6.7%) UBC cases, respectively. In 46 urine samples from patients with TERT promoter mutation-carrying tumors, the mutant promoter was detected in 24 (52%) prior to operation and disappeared in most examined urine samples (80%) taken 1 week after operation. TERT mRNA was detected in urine derived from 46 of 49 patients (94%) that was analyzed before operation independently of the presence of TERT promoter mutations. Collectively, FGFR3 mutations occur at a very low rate in Han Chinese UBC and cannot serve as diagnostic markers for Chinese patients. Han Chinese patients with UBC have relatively low TERT promoter mutation frequency compared with patients in Western countries, and simultaneous detection of both mutant TERT promoter and TERT mRNA improves sensitivity and specificity of urine-based diagnosis.

Deng Y, Bai H, Hu H
rs11671784 G/A variation in miR-27a decreases chemo-sensitivity of bladder cancer by decreasing miR-27a and increasing the target RUNX-1 expression.
Biochem Biophys Res Commun. 2015; 458(2):321-7 [PubMed] Related Publications
Single nucleotide polymorphism (SNP) rs11671784 is in the loop of pre-miR-27a and the G/A variation can significantly decrease mature miR-27a expression. This study explored the role of miR-27a in chemo-sensitivity of bladder cancer and how rs11671784 G/A variation affects the sensitivity. Blood and tumor samples from 89 bladder cancer cases were analyzed. In-vitro study was performed to explore the mechanism of chemo-sensitivity and the downstream target of miR-27a by using bladder cancer cell lines. This study identified a causative relationship between rs11671784 G/A variation, lowered miR-27a expression, increased RUNX-1 expression and following weakened chemo-sensitivity. rs11671784 G allele has significantly stronger effect over A allele in promoting chemo-sensitivity in bladder cancer. miR-27a mediates chemotherapy at least partially through reducing P-gp expression and increasing apoptosis. In addition, RUNX-1 is a novel direct target of miR-27a, which is involved in its regulation of chemo-sensitivity in bladder cancer.

Rose M, Schubert C, Dierichs L, et al.
OASIS/CREB3L1 is epigenetically silenced in human bladder cancer facilitating tumor cell spreading and migration in vitro.
Epigenetics. 2014; 9(12):1626-40 [PubMed] Related Publications
CREB3L1 has been recently proposed as a novel metastasis suppressor gene in breast cancer. Our current study highlights CREB3L1 expression, regulation, and function in bladder cancer. We demonstrate a significant downregulation of CREB3L1 mRNA expression (n = 64) in primary bladder cancer tissues caused by tumor-specific CREB3L1 promoter hypermethylation (n = 51). Based on pyrosequencing CREB3L1 methylation was shown to be potentially associated with a more aggressive phenotype of bladder cancer. These findings were verified by an independent public data set containing data from 184 bladder tumors. In addition, immunohistochemical evaluation showed that CREB3L1 protein expression is decreased in bladder cancer tissues as well. Interestingly, protein loss is predominately observed in the nuclei of aggressive tumor cells. Based on in vitro models we clearly show that CREB3L1 re-expression mediates suppression of tumor cell migration and colony growth of high grade and invasive bladder cancer cells. The candidate tumor suppressor and TGF-β signaling inhibitor HTRA3 was furthermore identified as putative target gene of CREB3L1 in both invasive J82 bladder cells and primary bladder tumors. Hence, our data provide for the first time evidence that the transcription factor CREB3L1 may have an important role as a putative tumor suppressor in bladder cancer.

Fang CY, Tsai YD, Lin MC, et al.
Inhibition of human bladder cancer growth by a suicide gene delivered by JC polyomavirus virus-like particles in a mouse model.
J Urol. 2015; 193(6):2100-6 [PubMed] Related Publications
PURPOSE: Bladder cancer is one of the most common cancers of the urinary tract. The poor 5-year survival rate of invasive bladder cancer represents a challenge for bladder cancer treatment. Previous studies demonstrated that human urothelial carcinoma is susceptible to infection by JC polyomavirus. We used JC polyomavirus virus-like particles to deliver genes into human urothelial carcinoma cells for possible therapeutic investigation.
MATERIALS AND METHODS: Reporter plasmids (pEGFP-N3) for expressing green fluorescent protein, LacZ expression plasmids bearing cytomegalovirus or Muc1 promoter and a functional plasmid (pUMVC1-tk) for expressing thymidine kinase were packaged into JC polyomavirus virus-like particles. Plasmid DNAs were transduced via the JC polyomavirus virus-like particles into human urothelial carcinoma cells in vitro and into xenografted human bladder tumor nodules in vivo.
RESULTS: pEGFP-N3 DNA was delivered and green fluorescent protein was expressed in human urothelial carcinoma cells in vitro and in the tumor nodules of mice in vivo. The thymidine kinase transgene also functioned in vitro and in vivo after JC polyomavirus virus-like particle transduction. The thymidine kinase gene transduced urothelial carcinoma nodules were drastically reduced in the presence of acyclovir. In addition, we noted selective Muc1-LacZ expression in human urothelial carcinoma cells transduced by JC polyomavirus virus-like particles.
CONCLUSIONS: These findings provide a possible future approach to human urothelial carcinoma gene therapy using JC polyomavirus virus-like particles.

Zhang Y, Yang D, Zhu JH, et al.
The association between NQO1 Pro187Ser polymorphism and urinary system cancer susceptibility: a meta-analysis of 22 studies.
Cancer Invest. 2015; 33(2):39-40 [PubMed] Related Publications
Numerous studies have investigated the association between NQO1 Pro187Ser polymorphism and urinary system cancer risk, but the findings are inconsistent. To derive a more precise estimation of such association, we performed a meta-analysis based on 22 publications encompassing 5,274 cases and 6,459 controls. Overall, significant association was found between NQO1 Pro187Ser polymorphism and urinary system cancer risk. Moreover, stratified analysis observed a statistically significant association for bladder cancer, prostate cancer, renal cell carcinoma, Caucasians, Asians, and hospital-based studies. In summary, this meta-analysis indicated that NQO1 Pro187Ser polymorphism conferred genetic susceptibility to urinary system cancer.

Jin Y, Lu J, Wen J, et al.
Regulation of growth of human bladder cancer by miR-192.
Tumour Biol. 2015; 36(5):3791-7 [PubMed] Related Publications
The regulation of microRNA-192 (miR-192) is impaired in many cancers. Here, we investigated the role of miR-192 in the proliferation, cell cycle progression, and apoptosis of bladder cancer cells. Human bladder cancer cells were transfected with human miR-192 precursor or non-specific control miRNA. The effect of miR-192 on cell proliferation was assessed by a MTT assay. The effects of miR-192 on cell cycle regulation and apoptosis were evaluated by flow cytometry. Western blot was used to analyze the protein levels of cyclin D1, p21, p27, Bcl-2, Bax, and Mcl-1. We found that overexpression of miR-192 significantly decreased the proliferation of bladder cancer cells by 22 and 54 % at 48 and 72 h, respectively. MiR-192-overexpressing cells exhibited a significant increase in G0/G1 phase and a significant decrease in S phase compared to the control miRNA-transfected cells. Moreover, overexpression of miR-192 significantly induced apoptotic death in bladder cancer cells, increased the levels of p21, p27, and Bax, and decreased the levels of cyclin D1, Bcl-2, and Mcl-1. Taken together, these data suggest that miR-192 may be a suppressor for bladder cancer cells by cell cycle regulation.

Miremami J, Kyprianou N
The promise of novel molecular markers in bladder cancer.
Int J Mol Sci. 2014; 15(12):23897-908 [PubMed] Article available free on PMC after 01/03/2016 Related Publications
Bladder cancer is the fourth most common malignancy in the US and is associated with the highest cost per patient. A high likelihood of recurrence, mandating stringent surveillance protocols, has made the development of urinary markers a focus of intense pursuit with the hope of decreasing the burden this disease places on patients and the healthcare system. To date, routine use of markers is not recommended for screening or diagnosis. Interests include the development of a single urinary marker that can be used in place of or as an adjunct to current screening and surveillance techniques, as well identifying a molecular signature for an individual's disease that can help predict progression, prognosis, and potential therapeutic response. Markers have shown potential value in improving diagnostic accuracy when used as an adjunct to current modalities, risk-stratification of patients that could aid the clinician in determining aggressiveness of surveillance, and allowing for a decrease in invasive surveillance procedures. This review discusses the current understanding of emerging biomarkers, including miRNAs, gene signatures and detection of circulating tumor cells in the blood, and their potential clinical value in bladder cancer diagnosis, as prognostic indicators, and surveillance tools, as well as limitations to their incorporation into medical practice.

Knowles MA, Hurst CD
Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity.
Nat Rev Cancer. 2015; 15(1):25-41 [PubMed] Related Publications
Urothelial carcinoma of the bladder comprises two long-recognized disease entities with distinct molecular features and clinical outcome. Low-grade non-muscle-invasive tumours recur frequently but rarely progress to muscle invasion, whereas muscle-invasive tumours are usually diagnosed de novo and frequently metastasize. Recent genome-wide expression and sequencing studies identify genes and pathways that are key drivers of urothelial cancer and reveal a more complex picture with multiple molecular subclasses that traverse conventional grade and stage groupings. This improved understanding of molecular features, disease pathogenesis and heterogeneity provides new opportunities for prognostic application, disease monitoring and personalized therapy.

Dip N, Reis ST, Abe DK, et al.
Micro RNA expression and prognosis in low-grade non-invasive urothelial carcinoma.
Int Braz J Urol. 2014 Sep-Oct; 40(5):644-9 [PubMed] Related Publications
PURPOSE: To analyze a possible correlation between a miRNA expression profile and important prognostic factors for pTa urothelial carcinomas (UC), including tumor size, multiplicity and episodes of recurrence.
MATERIALS AND METHODS: Thirty low-grade non-invasive pTa bladder UC from patients submitted to transurethral resection were studied, in a mean follow-up of 17.7 months. As controls, we used normal bladder tissue from five patients submitted to retropubic prostatectomy to treat benign prostatic hyperplasia. Extraction, cDNA and amplification were performed for 14 miRNAs (miR-100, -10a, -21, -205, -let7c, -143, -145, -221, -223, -15a, -16, -199a and -452) using specific kits, and RNU-43 and -48 were used as endogenous controls. Statistical tests were used to compare tumor size, multiplicity and episodes of recurrence with miRNAs expression profiles.
RESULTS: There was a marginal correlation between multiplicity and miR-let7c over-expression. For all others miRNA no correlation between their expression and prognostic factors was found.
CONCLUSION: We did not find differences for miRNAs expression profiles associated with prognostic factors in tumor group studied. The majority of miRNAs are down-regulated, except mir-10a, over-expressed in most of cases, seeming to have increased levels as tumor with more unfavorable prognostic factors. More studies are needed in order to find a miRNA profile able to provide prognosis in pTa UC to be used in clinical practice.

Zhou Z, Guo Y, Liu Y, et al.
Methylation-mediated silencing of Dlg5 facilitates bladder cancer metastasis.
Exp Cell Res. 2015; 331(2):399-407 [PubMed] Related Publications
UNLABELLED: Dlg5 (Discs large homolog 5), a member of the membrane-associated guanylate kinase adaptor family of scaffolding proteins, has been shown to participate in cancer progression. However, little is known about whether abnormal expression of Dlg5 facilitates bladder cancer metastasis. In the current study we initiated a study analyzing Dlg5 expression and its roles in human bladder cancer metastasis. The expression of Dlg5 is decreased in most bladder cancer tissues compared with adjacent normal tissues, and Dlg5 expression is further downregulated in patients with muscle-invasive tumors. DNA methylation analysis showed a methylation of Dlg5 gene in bladder cancer cell lines and in bladder cancer tumors, especially in muscle-invasive tumors. Hypermethylation of Dlg5 in bladder tumors is tightly correlated with silencing of Dlg5 expression, which is further functionally validated by demethylation analysis in bladder cancer cell lines. Knockdown of Dlg5 increases cancer cell invasion in vitro and promotes cancer metastasis in vivo. Of clinical significance, Kaplan-Meier analysis showed that downregulation of Dlg5 is significantly associated with reduced overall survival in patients with bladder cancer.
CONCLUSION: These data suggest that inhibition of Dlg5 by DNA hypermethylation contributes to provoke invasive phenotypes in bladder tumor.

Shen Y, Bu M, Zhang A, et al.
Toll-like receptor 4 gene polymorphism downregulates gene expression and involves in susceptibility to bladder cancer.
Tumour Biol. 2015; 36(4):2779-84 [PubMed] Related Publications
Bladder cancer is the ninth most frequent malignancy in China. Toll-like receptor 4 (TLR4) is expressed on various cells and greatly involves in immune responses. Genetic polymorphism may affect the pathogenesis of diseases through various pathways. In the current study, we evaluated the association between genetic polymorphisms in TLR4 and risk of bladder cancer. We also examined the effect of the polymorphisms on gene expression. The TLR4 -729G/C and -260G/C polymorphisms were genotyped in 282 bladder cancer patients and 298 healthy controls in the Chinese population. Results showed that subjects with -729GC genotype are at significantly higher risk of bladder cancer than those with GG genotype [odds ratio (OR) = 2.50, 95% confidence interval (CI) = 1.39-4.48, P = 0.002]. Similarly, TLR4 -729C allele revealed a positive association with the disease (OR = 2.39, P = 0.002). The other polymorphism, TLR4 -260G/C, did not present clear correlations with bladder cancer. To understand the function of the polymorphisms, we evaluated TLR4 messenger RNA (mRNA) and protein levels in CD4+ T cells, CD8+ T cells, and monocytes from subjects carrying different TLR4 genotypes. Results revealed that subjects carrying -729GC genotype had significantly downregulated mRNA and protein levels of TLR4 in CD4+ T cells, CD8+ T cells, and monocytes compared to those carrying GG genotype. However, subjects with -260G/C polymorphism did not show any differences in gene expression from immune cells These data suggest that TLR4 polymorphism is associated with increased susceptibility to bladder cancer possibly by downregulating gene expression in various immune cells.

Sun WX, Chen YH, Liu ZZ, et al.
Association between the CYP1A2 polymorphisms and risk of cancer: a meta-analysis.
Mol Genet Genomics. 2015; 290(2):709-25 [PubMed] Related Publications
The previously published data on the association between CYP1A2*1C (rs2069514) and CYP1A2*1F (rs762551) polymorphisms and cancer risk have remained controversial. Hence, we performed a meta-analysis to investigate the association between CYP1A2*1F and CYP1A2*1C polymorphisms and cancer risk under different inheritance models. Overall, significant association was observed between CYP1A2*1F and cancer risk when all the eligible studies were pooled into the meta-analysis (dominant model: OR 1.08, 95 % CI 1.02-1.15; heterozygous model: OR 1.06, 95 % CI 1.01-1.12; additive model: OR 1.07, 95 % CI 1.02-1.13). In the further stratified and sensitivity analyses, for CYP1A2*1F polymorphism, significantly increased lung cancer risk and significantly decreased bladder cancer risk were observed in Caucasians. For CYP1A2*1C polymorphism, no significant association was found in overall and all subgroup analyses. In summary, this meta-analysis suggests that CYP1A2*1F polymorphism is associated with lung cancer and bladder cancer risk in Caucasians.

Biton A, Bernard-Pierrot I, Lou Y, et al.
Independent component analysis uncovers the landscape of the bladder tumor transcriptome and reveals insights into luminal and basal subtypes.
Cell Rep. 2014; 9(4):1235-45 [PubMed] Related Publications
Extracting relevant information from large-scale data offers unprecedented opportunities in cancerology. We applied independent component analysis (ICA) to bladder cancer transcriptome data sets and interpreted the components using gene enrichment analysis and tumor-associated molecular, clinicopathological, and processing information. We identified components associated with biological processes of tumor cells or the tumor microenvironment, and other components revealed technical biases. Applying ICA to nine cancer types identified cancer-shared and bladder-cancer-specific components. We characterized the luminal and basal-like subtypes of muscle-invasive bladder cancers according to the components identified. The study of the urothelial differentiation component, specific to the luminal subtypes, showed that a molecular urothelial differentiation program was maintained even in those luminal tumors that had lost morphological differentiation. Study of the genomic alterations associated with this component coupled with functional studies revealed a protumorigenic role for PPARG in luminal tumors. Our results support the inclusion of ICA in the exploitation of multiscale data sets.

Kang Z, Li Y, Yu Y, Guo Z
Research progress on bladder cancer molecular genetics.
J Cancer Res Ther. 2014; 10 Suppl:C89-94 [PubMed] Related Publications
Bladder cancer is a common malignant urinary tumor with a high rate of recurrence and quick progression, which threats human health. With the research on bladder cancer molecular genetics, the knowledge of gene modification and the development of molecular detection methods, more tumor markers have been discovered, which may have potential for early diagnosis, clinical examination and prognosis. This article reviews the research progress on bladder cancer molecular genetics.

Lv L, Li Y, Deng H, et al.
MiR-193a-3p promotes the multi-chemoresistance of bladder cancer by targeting the HOXC9 gene.
Cancer Lett. 2015; 357(1):105-13 [PubMed] Related Publications
Chemoresistance prevents the curative cancer chemotherapy and presents a formidable challenge for both cancer researchers and clinicians. We have previously shown that miR-193a-3p promotes the multi-chemoresistance of bladder cancer cells via repressing its three target genes: SRSF2, PLAU and HIC2. Here, we showed that as a new direct target, the homeobox C9 (HOXC9) gene also executes the promoting effect of miR-193a-3p on the bladder cancer chemoresistance from a systematic study of multi-chemosensitive (5637) and resistant (H-bc) bladder cancer cell lines in both cell culture and tumor-xenograft/nude mice system. Paralleled with the changes in the drug-triggered cell death, the activities of both DNA damage response and oxidative stress pathways were drastically altered by a forced reversal of miR-193a-3p or HOXC9 levels in bladder cancer cells. In addition to a new mechanistic insight, our results provide a set of the essential genes in the miR-193a-3p/HOXC9/DNA damage response/oxidative stress pathway axis as the diagnostic targets for the guided anti-bladder cancer chemotherapy.

Schulz WA, Koutsogiannouli EA, Niegisch G, Hoffmann MJ
Epigenetics of urothelial carcinoma.
Methods Mol Biol. 2015; 1238:183-215 [PubMed] Related Publications
Urothelial carcinoma is the most frequent type of bladder cancer. Improvements in diagnostics and therapy of this common tumor are urgently required and need to be based on a better understanding of its biology. Epigenetic aberrations are crucial to urothelial carcinoma development and progression. They affect DNA methylation, histone modifications, chromatin remodeling, long noncoding RNAs, and microRNAs. Compared to other cancers, DNA hypomethylation, especially at LINE-1 retrotransposons, and mutations in enzymes establishing or removing histone acetylation or methylation are particularly prominent. Accumulating evidence suggests that disturbances in DNA methylation, histone modifications and noncoding RNAs may contribute especially to altered differentiation and metastatic potential. With proper selection, histone-modifying enzymes may constitute good targets for therapy. For diagnostics, DNA methylation and miRNA biomarkers are well suited because of their relatively high stability. There are indeed excellent biomarker candidates for DNA-methylation-based diagnostics of urothelial carcinoma, whereas miRNAs are well investigated, but there are still many discrepancies between studies published to date.

Huang K, Chen G, Luo J, et al.
Clinicopathological and cellular signature of PAK1 in human bladder cancer.
Tumour Biol. 2015; 36(4):2359-68 [PubMed] Related Publications
Bladder cancer (BC) is the ninth most common cancer and the 13th most common cause of cancer death. Although p21 protein-activated kinase (PAK) regulates cell growth, motility, and morphology, the expression and function of PAK1 associated with the clinicopathological and cellular signature of human BC are not clear. This study was to examine the expression of PAK1 in human BC, the association of PAK1 with clinicopathological features, and the effect of PAK1 on cell proliferation, migration, and invasion in BC cells. A total of 54 BC and 12 normal bladder tissue specimens were retrieved. Among 54 BC patients, 39 cases were superficial BC and 15 cases were invasive BC. Histological examination revealed 29 patients with low-grade and 25 patients with high-grade papillary urothelial carcinomas. Immunohistochemical staining showed that PAK1 was overexpressed in BC tissue compared with normal bladder tissue. The overexpression of PAK1 was significantly associated with tumor size, histological grade, and lymph node metastasis, but not with gender, age, clinical stage, tumor number, and recurrence. Furthermore, the cytoplasmic distribution of PAK1 was observed in BC cells. Knocking down of PAK1 using lentiviral transduction decreased BC cell proliferation, migration, and invasion. In conclusion, we demonstrated that the overexpression of PAK1 is closely associated with the clinicopathological features of BC, suggesting that PAK1 may play an important role in the development and progression of BC and may be a potential therapeutic target for the treatment of BC.

Bonberg N, Pesch B, Behrens T, et al.
Chromosomal alterations in exfoliated urothelial cells from bladder cancer cases and healthy men: a prospective screening study.
BMC Cancer. 2014; 14:854 [PubMed] Article available free on PMC after 01/03/2016 Related Publications
BACKGROUND: Chromosomal instability in exfoliated urothelial cells has been associated with the development of bladder cancer. Here, we analyzed the accumulation of copy number variations (CNVs) using fluorescence in situ hybridization in cancer cases and explored factors associated with the detection of CNVs in tumor-free men.
METHODS: The prospective UroScreen study was designed to investigate the performance of UroVysion™ and other tumor tests for the early detection of bladder cancer in chemical workers from 2003-2010. We analyzed a database compiling CNVs of chromosomes 3, 7, and 17 and at 9p21 that were detected in 191,434 exfoliated urothelial cells from 1,595 men. We assessed the accumulation of CNVs in 1,400 cells isolated from serial samples that were collected from 18 cancer cases up to the time of diagnosis. A generalized estimating equation model was applied to evaluate the influence of age, smoking, and urine status on CNVs in cells from tumor-free men.
RESULTS: Tetrasomy of chromosomes 3, 7 and 17, and DNA loss at 9p21 were the most frequently observed forms of CNV. In bladder cancer cases, we observed an accumulation of CNVs that started approximately three years before diagnosis. During the year prior to diagnosis, cells from men with high-grade bladder cancer accumulated more CNVs than those obtained from cases with low-grade cancer (CNV < 2: 7.5% vs. 1.1%, CNV > 2: 16-17% vs. 9-11%). About 1% of cells from tumor-free men showed polysomy of chromosomes 3, 7, or 17 or DNA loss at 9p21. Men aged ≥50 years had 1.3-fold more cells with CNVs than younger men; however, we observed no further age-related accumulation of CNVs in tumor-free men. Significantly more cells with CNVs were detected in samples with low creatinine concentrations.
CONCLUSIONS: We found an accumulation of CNVs during the development of bladder cancer starting three years before diagnosis, with more altered cells identified in high-grade tumors. Also, a small fraction of cells with CNVs were exfoliated into urine of tumor-free men, mainly exhibiting tetraploidy or DNA loss at 9p21. Whether these cells are preferentially cleared from the urothelium or are artifacts needs further exploration.

Li LJ, Zhu JL, Bao WS, et al.
Long noncoding RNA GHET1 promotes the development of bladder cancer.
Int J Clin Exp Pathol. 2014; 7(10):7196-205 [PubMed] Article available free on PMC after 01/03/2016 Related Publications
In spite of the advances in the diagnosis and treatment of bladder cancer, the prognosis of bladder cancer remains relatively poor. As a result, it is vital to identify novel diagnostic and prognostic marker of bladder cancer. A growing volume of literature has implicated the vital role of long noncoding RNA in the development of cancer. GHET1, a recently identified lncRNA, was initially characterized in gastric cancer. However, its role in bladder cancer remains largely unknown. In this study, we demonstrated that GHET1 was upregulated in bladder cancer tissues compared to adjacent normal tissues and its over-expression correlates with tumor size, advanced tumor and lymph node status, and poor survival. GHET1 knockdown suppressed the proliferation and invasion of bladder cancer cells in vitro. In the meantime, inhibition of GHET1 reversed the epithelial-mesenchymal-transition in bladder cancer cell line. Taken together, our study suggests that the potential use of GHET1 as a prognostic marker and therapeutic target of bladder cancer.

Lee JH, Song HR, Kim HN, et al.
Genetic variation in PSCA is associated with bladder cancer susceptibility in a Korean population.
Asian Pac J Cancer Prev. 2014; 15(20):8901-4 [PubMed] Related Publications
BACKGROUND: Genetic factors play important roles in the pathogenesis of human cancer. A recent genome wide association study (GWAS) identified an association between the rs2294008 polymorphism of the prostate stem cell antigen (PSCA) gene and bladder cancer risk in Caucasians. The aim of this study was to determine whether the rs2294008 polymorphism is similarly associated with bladder cancer susceptibility in a Korean population.
MATERIALS AND METHODS: We conducted a case-control study of 411 bladder cancer patients and 1,700 controls.
RESULTS: The frequencies of the CC, CT, and TT genotypes of the rs2294008 polymorphism were 16.9, 54.0, and 28.8% in bladder cancer patients and 24.4, 48.1, and 27.5% in controls, respectively. We found that the combined CT/TT genotypes were associated with a significantly increased risk of bladder cancer (OR CT/TT=1.58, 95% CI=1.15-2.17), compared with the CC genotype. Smoking habits, tumor grade and tumor stage did not modify the association between rs2294008 and the risk of bladder cancer.
CONCLUSIONS: Our study showed that the rs2294008 polymorphism in the PSCA gene is associated with the risk of bladder cancer in a Korean population, providing evidence that it may contribute to bladder carcinogenesis regardless of ethnicity.


The NOTCH pathway plays a tumor suppressive role in bladder cancer.
Cancer Discov. 2014; 4(11):1252 [PubMed] Related Publications
Inactivation of the NOTCH pathway drives bladder tumorigenesis.

Zhang Y, Sun Y, Chen T, et al.
Genetic variations rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population.
Int J Mol Sci. 2014; 15(11):19330-41 [PubMed] Article available free on PMC after 01/03/2016 Related Publications
Genome-wide association studies (GWAS) have identified a number of genetic variants associated with risk of bladder cancer in populations of European descent. Here, we assessed association of two of these variants, rs11892031 (2q37.1 region) and rs401681 (5p15.33 region) in a Chinese case-control study, which included 367 bladder cancer cases and 420 controls. We found that the AC genotype of rs11892031 was associated with remarkably decreased risk of bladder cancer (adjusted odds ratio (OR), 0.27; 95% confidence interval (CI), 0.09-0.81; p=0.019), compared with the AA genotype of rs11892031; and that CT/CC genotypes of rs401681 were associated with significantly increased risk of bladder cancer (adjusted OR, 1.79; 95% CI, 1.10-2.91; p=0.02), compared with the TT genotype of rs401681. We further conducted stratification analysis to examine the correlation between single nucleotide polymorphism (SNP) rs11892031/rs401681 and tumor grade/stage. Results showed that heterogeneity in ORs of tumor categories was not significant for either rs11892031 or rs401681 (p>0.05), indicating that the two SNPs seemingly do not associate with tumor grade and stage of bladder cancer in our study population. The present study suggests that the SNPs rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population. Future analyses will be conducted with more participants recruited in a case-control study.

Recurrent Chromosome Abnormalities

Selected list of common recurrent structural abnormalities

This is a highly selective list aiming to capture structural abnormalies which are frequesnt and/or significant in relation to diagnosis, prognosis, and/or characterising specific cancers. For a much more extensive list see the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer.

Chromosome Y Loss in Bladder Cancer

Khaled HM, Aly MS, Magrath IT
Loss of Y chromosome in bilharzial bladder cancer.
Cancer Genet Cytogenet. 2000; 117(1):32-6 [PubMed] Related Publications
Bilharzial bladder cancer is the most common malignant neoplasm in Egypt, also occurring with a high incidence in other regions of the Middle East and East Africa. In a previous study, using centromere probes specific for chromosomes 3, 4, 7-11, 16, and 17, we demonstrated that monosomy of chromosome 9 (48.4%), and numerical aberrations of chromosome 17 (19.4%) were the most common observed imbalances. The present study extends the establishment of the baseline cytogenetic profile of this type of malignancy. Interphase cytogenetics by fluorescence in situ hybridization with the use of a panel of centromere-associated DNA probes for chromosomes 1, 2, 5, 6, 12, 13/21, 14, 15, 18, 19, 20, X, and Y was performed on paraffin-embedded bladder specimens from 25 Egyptian patients affected with bilharzial bladder cancer. No numerical aberrations were detected in the 25 cases for chromosomes 1, 2, 5, 6, 12, 13/21, 14, 15, 18, 19, 20, and X. However, loss of chromosome Y was observed in 7 of the 17 male cases studied (41.2%). No significant correlation was observed between loss of the Y chromosome and any of the different clinicopathologic characteristics of these cases. These data suggest that loss of the Y chromosome is the second frequent event that can occur in bilharzial bladder cancer. A molecular genetic model of bilharzial bladder cancer is evolving.

Sauter G, Moch H, Wagner U, et al.
Y chromosome loss detected by FISH in bladder cancer.
Cancer Genet Cytogenet. 1995; 82(2):163-9 [PubMed] Related Publications
To examine the significance of Y chromosome losses in bladder cancer, fluorescence in situ hybridization (FISH) was used to determine its prevalence and associations with known parameters of malignancy. Cells were dissociated from formalin-fixed paraffin-embedded bladder tumors from 68 male patients and from 11 post-mortem bladder washes of male patients with a negative bladder cancer history, and were examined by FISH using centromeric probes for chromosomes X, Y, 7, 9, and 17. Nullisomy for chromosome Y was seen in 23 of 68 tumors (34%), monosomy in 28 of 68 tumors (41%), and polysomy in 17 of 68 tumors (25%). There was no association between chromosome Y loss and tumor grade, stage, tumor growth fraction (Ki67 LI), p53 immunostaining, and presence of p53 deletions. Patient age was higher for tumors with a Y loss (73.5 +/- 12.0 years) than for tumors without Y loss (66.6 +/- 10.8 years; p = 0.0207). In one normal bladder wash, a distinct subpopulation (38% of cells) with Y nullisomy was seen. These data suggest that Y loss is a frequent event that can occur early in bladder cancer, although there is no evidence for a role of Y loss in tumor progression.

del(9q) in Bladder Cancer

Loss of heterozygosity (LOH) on chromosome arm 9 is the most frequent genetic alteration in transitional cell carcinomas. Candidate tumor suppressor genes/loci have been proposed, including: CDKN2 and DBCCR1.

Habuchi T, Yoshida O, Knowles MA
A novel candidate tumour suppressor locus at 9q32-33 in bladder cancer: localization of the candidate region within a single 840 kb YAC.
Hum Mol Genet. 1997; 6(6):913-9 [PubMed] Related Publications
Loss of heterozygosity (LOH) on chromosome 9q is the most frequent genetic alteration in transitional cell carcinoma (TCC) of the bladder, implicating the presence of a tumour suppressor gene or genes on 9q. To define the location of a tumour suppressor locus on 9q in TCC, we screened 156 TCCs of the bladder and upper urinary tract by detailed deletion mapping using 31 microsatellite markers on 9q. Partial deletions of 9q were found in 10 TCCs (6%), and LOH at all informative loci on 9q was found in 77 TCCs (49%). In five low grade superficial bladder tumours, the partial deletion was localized to D9S195 located at 9q32-33, with retention of heterozygosity at all other informative loci including D9S103, D9S258, D9S275 and GSN. We constructed a yeast artificial chromosome (YAC) contig covering the deleted region in these five tumours and placed another four unmapped microsatellite markers on this contig map. Using these markers, we further defined the common deleted region to the interval between D9S1848 and AFMA239XA9. The region is covered by a single YAC (852e11), whose size is estimated to be 840 kb. Our data should expedite further fine mapping and identification of the candidate tumour suppressor gene at 9q32-33.

Habuchi T, Luscombe M, Elder PA, Knowles MA
Structure and methylation-based silencing of a gene (DBCCR1) within a candidate bladder cancer tumor suppressor region at 9q32-q33.
Genomics. 1998; 48(3):277-88 [PubMed] Related Publications
Loss of heterozygosity (LOH) on chromosome 9q is the most frequent genetic alteration in transitional cell carcinoma (TCC) of the bladder, indicating the presence of one or more relevant tumor suppressor genes. We previously mapped one of these putative tumor suppressor loci to 9q32-q33 and localized the candidate region within a single YAC 840 kb in size. This locus has been designated DBC1 (for deleted in bladder cancer gene 1). We have identified a novel gene, DBCCR1, in this candidate region by searching for expressed sequence tags (ESTs) that map to YACs spanning the region. Database searching using the entire DBCCR1 cDNA sequence identified several human ESTs and a few homologous mouse. ESTs. However, the predicted 761-amino-acid sequence had no significant homology to known protein sequences. Mutation analysis of the coding region and Southern blot analysis detected neither somatic mutations nor gross genetic alterations in primary TCCs. Although DBCCR1 was expressed in multiple normal human tissues including urothelium, mRNA expression was absent in 5 of 10 (50%) bladder cancer cell lines. Methylation analysis of the CpG island at the 5' region of the gene and the induction of de novo expression by a demethylating agent indicated that this island might be a frequent target for hypermethylation and that hypermethylation-based silencing of the gene occurs in TCC. These findings make DBCCR1 a good candidate for DBC1.

Knowles MA
Identification of novel bladder tumour suppressor genes.
Electrophoresis. 1999; 20(2):269-79 [PubMed] Related Publications
Many genetic alterations have recently been identified in transitional cell carcinoma (TCC) of the bladder. These include alterations to known proto-oncogenes and tumour suppressor genes and the identification of multiple sites of nonrandom chromosomal deletion which are predicted to define the location of as yet unidentified tumour suppressor genes. This review summarises recent efforts to define the location of novel bladder tumour suppressor genes using loss of heterozygositiy (LOH) and homozygous deletion analyses and to isolate the genes targeted by these deletions. For three of the four regions of deletion on chromosome 9, the most frequently deleted chromosome in TCC, candidate genes have been identified. It is anticipated that the identification of the genes and/or genetic regions which are frequently altered in TCC will provide useful tools for diagnosis, prediction of prognosis, patient monitoring and novel therapies.

van Tilborg AA, Groenfeld LE, van der Kwast TH, Zwarthoff EC
Evidence for two candidate tumour suppressor loci on chromosome 9q in transitional cell carcinoma (TCC) of the bladder but no homozygous deletions in bladder tumour cell lines.
Br J Cancer. 1999; 80(3-4):489-94 [PubMed] Free Access to Full Article Related Publications
The most frequent genetic alterations in transitional cell carcinoma (TCC) of the bladder involve loss of heterozygosity (LOH) on chromosome 9p and 9q. The LOH on chromosome 9p most likely targets the CDKN2 locus, which is inactivated in about 50% of TCCs. Candidate genes that are the target for LOH on chromosome 9q have yet to be identified. To narrow the localization of one or more putative tumour suppressor genes on this chromosome that play a role in TCC of the bladder, we examined 59 tumours with a panel of microsatellite markers along the chromosome. LOH was observed in 26 (44%) tumours. We present evidence for two different loci on the long arm of chromosome 9 where potential tumour suppressor genes are expected. These loci are delineated by interstitial deletions in two bladder tumours. Our results confirm the results of others and contribute to a further reduction of the size of these regions, which we called TCC1 and TCC2. These regions were examined for homozygous deletions with EST and STS markers. No homozygous deletions were observed in 17 different bladder tumour cell lines.

Simoneau M, Aboulkassim TO, LaRue H, et al.
Four tumor suppressor loci on chromosome 9q in bladder cancer: evidence for two novel candidate regions at 9q22.3 and 9q31.
Oncogene. 1999; 18(1):157-63 [PubMed] Related Publications
The most common genetic alteration identified in transitional cell carcinoma (TCC) of the bladder is loss of heterozygosity (LOH) on chromosome 9. However, localization of tumor suppressor genes on 9q has been hampered by the low frequency of subchromosomal deletions. We have analysed 139 primary, initial low stage TCC of the bladder using a panel of 28 microsatellite markers spanning chromosome 9 at an average distance of 5 Mb, following a primer-extension preamplification (PEP) technique. Sixty-seven (48%) tumors showed LOH at one or more loci and partial deletions were detected in 62 (45%) tumors; apparent monosomy 9 was detected in only five (4%) tumors. Deletions were more frequent on 9q (44%) than on 9p (23%), the latter being mostly associated with 9q deletion, suggesting that alteration of genes on 9q may be an early event associated with superficial papillary tumors. Combined data from the cases with partial 9q deletions displayed four candidate regions for tumor suppressor loci, based on the frequency of deletion observed and tumors with unique deletions at these sites. In two tumors, the unique partial deletion comprised D9S12 at 9q22.3, a region encompassing loci for the Gorlin syndrome and multiple self-healing squamous epithelioma gene. In two other tumors, the single LOH was identified at the D9S172 locus at 9q31-32 where the dysautonia and Fukuyama-type congenital muscular dystrophy genes have been located. One tumor showed unique LOH at the GSN locus at 9q33, a region frequently deleted in other sporadic tumors while the fourth region of deletion was observed at 9q34 between ASS and ABL-1, in two tumors. This region is frequently deleted in tumors and encompasses the locus for the hereditary hemorrhagic telangiectasia gene. These findings suggest four target regions on 9q within which suppressor genes for TCC may reside.

Uroplakins and Bladder Cancer

Uroplakins are membrane proteins specific to mammalian urothelium. These are expressed in both normal and cancerous urothelium. Mutations have rarely been reported, however, uroplakins act as a useful marker for detecting metastases and circulating TCC cells. The uroplakin family includes: UKP1A, UKP1B, UKP2 and UKP3.
Moll R, Wu XR, Lin JH, Sun TT
Uroplakins, specific membrane proteins of urothelial umbrella cells, as histological markers of metastatic transitional cell carcinomas.
Am J Pathol. 1995; 147(5):1383-97 [PubMed] Free Access to Full Article Related Publications
Uroplakins (UPs) Ia, Ib, II, and III, transmembrane proteins constituting the asymmetrical unit membrane of urothelial umbrella cells, are the first specific urothelial differentiation markers described. We investigated the presence and localization patterns of UPs in various human carcinomas by applying immunohistochemistry (avidin-biotin-peroxidase complex method), using rabbit antibodies against UPs II and III, to paraffin sections. Positive reactions for UP III (sometimes very focal) were noted in 14 of the 16 papillary noninvasive transitional cell carcinomas (TCCs) (88%), 29 of the 55 invasive TCCs (53%), and 23 of the 35 TCC metastases (66%). Different localization patterns of UPs could be distinguished, including superficial membrane staining like that found in normal umbrella cells (in papillary carcinoma), luminal (microluminal) membrane staining (in papillary and invasive carcinoma), and, against expectations, peripheral membrane staining (in invasive carcinoma). Non-TCC carcinomas of various origins (n = 177) were consistently negative for UPs. The presence of UPs in metastatic TCCs represents a prime example of even advanced tumor progression being compatible with the (focal) expression of highly specialized differentiation repertoires. Although of only medium-grade sensitivity, UPs do seem to be highly specific urothelial lineage markers, thus operating up interesting histodiagnostic possibilities in cases of carcinoma metastases of uncertain origin.

Wu RL, Osman I, Wu XR, et al.
Uroplakin II gene is expressed in transitional cell carcinoma but not in bilharzial bladder squamous cell carcinoma: alternative pathways of bladder epithelial differentiation and tumor formation.
Cancer Res. 1998; 58(6):1291-7 [PubMed] Related Publications
Uroplakins (UPs) are integral membrane proteins that are synthesized as the major differentiation products of mammalian urothelium. We have cloned the human UP-II gene and localized it on chromosome 11q23. A survey of 50 transitional cell carcinomas (TCCs) revealed a UP-II polymorphism but no tumor-specific mutations. Immunohistochemical staining using rabbit antisera against a synthetic peptide of UP-II and against total UPs showed UP reactivity in 39.5% (17 of 43 cases) of conventional TCCs, 12.8% (5 of 39) of bilharzial-related TCCs, and 2.7% (1 of 36) of bilharzial-related squamous cell carcinomas (SCCs). The finding that fewer bilharzial TCCs express UPs than conventional TCCs (12.8 versus 40%) raised the possibility that the former are heterogeneous, expressing SCC features to varying degrees. Our data strongly support the hypothesis that urothelium can undergo at least three pathways of differentiation: (a) urothelium-type pathway; (b) epidermis-type pathway; and (c) glandular-type pathway, characterized by the production of UPs, K1/K10 keratins, and secreted glycoproteins, respectively. Vitamin A deficiency and mesenchymal factors may play a role in determining the relative contributions of these pathways to urothelial differentiation as well as to the formation of TCC, SCC, and adenocarcinoma, or a mixture thereof.

Yuasa T, Yoshiki T, Tanaka T, et al.
Expression of uroplakin Ib and uroplakin III genes in tissues and peripheral blood of patients with transitional cell carcinoma.
Jpn J Cancer Res. 1998; 89(9):879-82 [PubMed] Related Publications
Uroplakins (UPs), urothelium-specific transmembrane proteins, are present only in urothelial cells. We have determined the nucleotide sequences of human UP-Ib and UP-III and synthesized specific primer pairs. The two UP genes were expressed in both cancerous and noncancerous urothelial taken from all patients examined by reverse transcription-polymerase chain reaction (RT-PCR). These genes were also detected in the peripheral blood of 3 patients with metastatic transitional cell carcinoma (TCC), but not in that from 9 patients with non-metastatic TCC or 3 healthy volunteers. The sensitivity of our assay was sufficient to detect one cancer cell in 5 ml of peripheral blood. Detection of UP gene-expression in blood by RT-PCR may provide helpful information for the diagnosis and management of TCC.

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