Head and Neck Cancers - Molecular Biology

Overview

Literature Analysis

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

Mutated Genes and Abnormal Protein Expression (44)

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
CDKN2A 9p21 ARF, MLM, P14, P16, P19, CMM2, INK4, MTS1, TP16, CDK4I, CDKN2, INK4A, MTS-1, P14ARF, P19ARF, P16INK4, P16INK4A, P16-INK4A Prognostic
-CDKN2A Mutations in Head and Neck Cancer
446
GSTM1 1p13.3 MU, H-B, GST1, GTH4, GTM1, MU-1, GSTM1-1, GSTM1a-1a, GSTM1b-1b -GSTM1 and Head and Neck Cancers
248
GSTT1 22q11.23 -GSTT1 Polymorphisms and Head and Neck Cancer
169
PTGS2 1q25.2-q25.3 COX2, COX-2, PHS-2, PGG/HS, PGHS-2, hCox-2, GRIPGHS -PTSG2 (COX2) and Head and Neck Squamous Carcinoma
165
ALDH2 12q24.2 ALDM, ALDHI, ALDH-E2 -ALDH2 and Head and Neck Cancers
111
SDHD 11q23 PGL, CBT1, CWS3, PGL1, QPs3, SDH4, cybS, CII-4 -SDHD and Head and Neck Cancers
105
SDHB 1p36.1-p35 IP, SDH, CWS2, PGL4, SDH1, SDH2, SDHIP -SDHB and Head and Neck Cancers
91
NOTCH1 9q34.3 hN1, AOS5, TAN1, AOVD1 -NOTCH1 mutations in Head and Neck Cancers
80
TP63 3q28 AIS, KET, LMS, NBP, RHS, p40, p51, p63, EEC3, OFC8, p73H, p73L, SHFM4, TP53L, TP73L, p53CP, TP53CP, B(p51A), B(p51B) -TP63 and Head and Neck Cancers
70
SDHC 1q23.3 CYBL, PGL3, QPS1, SDH3, CYB560 -SDHC and Head and Neck Cancers
64
ADH1B 4q23 ADH2, HEL-S-117 -ADH1B and Head and Neck Cancers
51
MIR21 17q23.1 MIRN21, miR-21, miRNA21, hsa-mir-21 -MicroRNA miR-21 and Head and Neck Cancer
49
XRCC3 14q32.3 CMM6 -XRCC3 and Head and Neck Cancers
46
CTTN 11q13 EMS1 -CTTN and Head and Neck Cancers
34
VHL 3p25.3 RCA1, VHL1, pVHL, HRCA1 -VHL and Head and Neck Cancers
34
OGG1 3p26.2 HMMH, MUTM, OGH1, HOGG1 -OGG1 and Head and Neck Cancers
30
ADH1C 4q23 ADH3 -ADH1C and Head and Neck Cancers
30
NFIB 9p24.1 CTF, NF1-B, NFI-B, NFIB2, NFIB3, NF-I/B, NFI-RED, HMGIC/NFIB -NFIB and Head and Neck Cancers
28
CKAP4 12q23.3 p63, CLIMP-63, ERGIC-63 -CKAP4 and Head and Neck Cancers
27
CCNA1 13q12.3-q13 CT146 -CCNA1 and Head and Neck Cancers
20
PGLS 19p13.2 6PGL -PGLS and Head and Neck Cancers
20
TNFRSF10B 8p22-p21 DR5, CD262, KILLER, TRICK2, TRICKB, ZTNFR9, TRAILR2, TRICK2A, TRICK2B, TRAIL-R2, KILLER/DR5 -TNFRSF10B and Head and Neck Cancers
17
SDHAF2 11q12.2 PGL2, SDH5, C11orf79 -SDHAF2 and Head and Neck Cancers
15
S100A2 1q21 CAN19, S100L -S100A2 and Head and Neck Cancers
14
ERCC4 16p13.12 XPF, RAD1, FANCQ, ERCC11 -ERCC4 and Head and Neck Cancers
14
SDHA 5p15 FP, PGL5, SDH1, SDH2, SDHF, CMD1GG -SDHA and Head and Neck Cancers
13
TMEM127 2q11.2 -TMEM127 and Head and Neck Cancers
10
SLC5A8 12q23.1 AIT, SMCT, SMCT1 -SLC5A8 and Head and Neck Cancers
9
MTHFD1 14q24 MTHFC, MTHFD -MTHFD1 and Head and Neck Cancers
7
ADAM17 2p25 CSVP, TACE, NISBD, ADAM18, CD156B, NISBD1 -ADAM17 and Head and Neck Cancers
7
MAGEB2 Xp21.3 DAM6, CT3.2, MAGE-XP-2 -MAGEB2 and Head and Neck Cancers
7
CCL19 9p13 ELC, CKb11, MIP3B, MIP-3b, SCYA19 -CCL19 and Head and Neck Cancers
7
CIC 19q13.2 -CIC and Head and Neck Cancers
7
FAT1 4q35 FAT, ME5, CDHF7, CDHR8, hFat1 -FAT1 and Head and Neck Cancers
6
CYP2A13 19q13.2 CPAD, CYP2A, CYPIIA13 -CYP2A13 and Head and Neck Cancers
5
CSMD1 8p23.2 PPP1R24 -CSMD1 and Head and Neck Cancers
5
CD3D 11q23 T3D, IMD19, CD3-DELTA -CD3D and Head and Neck Cancers
4
ING3 7q31 Eaf4, ING2, MEAF4, p47ING3 -ING3 and Head and Neck Cancers
4
LIMD1 3p21.3 -LIMD1 and Head and Neck Cancers
3
SPECC1 17p11.2 NSP, CYTSB, HCMOGT1, HCMOGT-1 -SPECC1 and Head and Neck Cancers
2
MIR1271 5q35 MIRN1271, hsa-mir-1271 -MIRN1271 microRNA, human and Head and Neck Cancers
2
RHOBTB2 8p21.3 DBC2 -RHOBTB2 and Head and Neck Cancers
2
RNF213 17q25.3 ALO17, MYMY2, MYSTR, NET57, C17orf27, KIAA1618 -RNF213 and Head and Neck Cancers
1
KLK10 19q13 NES1, PRSSL1 -KLK10 and Tongue Neoplasms
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

Umair A, Tarakji B, Ibrahim A, et al.
Quantitative study of epigenetic signature in head and neck squamous cell carcinoma.
Turk J Med Sci. 2015; 45(2):372-86 [PubMed] Related Publications
BACKGROUND/AIM: The aberrant upregulation of Forkhead box protein M1 (FOXM1) plays a fundamental role in cancer initiation by perturbing stem cell differentiation. This study aims to investigate the role of FOXMI in epigenetic modification and gene expression of target genes in primary human oral keratinocytes, squamous cell carcinoma cell lines, and head and neck squamous cell carcinoma (HNSCC) tissue biopsies.
MATERIALS AND METHODS: A genome-wide promoter methylation microarray was used to compare HNSCC cell line (n = 8), primary human oral keratinocytes (NOK; n = 8) transduced with FOXM1 and EGFP, and HNSCC tissue biopsies (n = 3). Seventeen Foxm1B- induced differentially methylated genes were shortlisted. An absolute quantitative polymerase chain reaction was used to validate the differential promoter DNA methylation of each candidate gene induced by FOXML. These results were compared with the methylation status and altered gene expressions of candidate genes in a panel of genomic DNA and messenger RNA (mRNA) samples previously extracted from HNSCC tissue biopsies.
RESULTS: The results were consistent with our hypothesis, showing that aberrant. upregulation of FOXM1 expression in in vitro primary NOK induces a global hypomethylation pattern similar to the HNSCC cell line and has an inverse correlation with in vivo mRNA expression levels of HNSCC tissue biopsy.
CONCLUSION: Such epigenetic changes have tremendous clinical potential as biomarkers for early cancer detection and therapeutic interventions.

Mutlu P, Mutlu M, Yalcin S, et al.
Detection of XRCC1 gene polymorphisms in Turkish head and neck squamous cell carcinoma patients: a comparative analysis with different populations.
J BUON. 2015 Mar-Apr; 20(2):540-7 [PubMed] Related Publications
PURPOSE: X-ray repair cross-complementing (XRCC1) is one of the most important genes for the maintenance of genomic integrity and protection of cells from DNA damage. Although tobacco and alcohol consumption are the major risk factors for the development of head and neck squamous cell carcinoma (HNSCC), sequence variation in XRCC1 gene may alter HNSCC susceptibility. Reports on the relationship between HNSCC and polymorphisms in XRCC1 gene have been inconsistent so far. The aim of this study was to investigate the association of XRCC1 Arg194Trp and Arg399Gln single nucleotide polymorphisms (SNP), smoking and alcohol consumption with the risk of HNSCC in Turkish population and also to compare to these results with the ones from both Turkish and different populations in the literature. The frequencies of Arg194Trp and Arg399Gln SNPs were studied in 55 HNSCC and 69 healthy individuals.
METHODS: Genomic DNA was isolated from peripheral blood and SNP was genotyped by PCR-RFLP method.
RESULTS: The genotype and allele frequencies of both polymorphisms were not statistically different between the HNSCC and control groups. On the other hand, smoking and chronic alcohol consumption were associated with risk of HNSCC, but there was no association between Arg194Trp, Arg399Gln polymorphisms, smoking and alcohol consumption in HNSCC cases.
CONCLUSION: These results indicate that both Arg194Trp and Arg399Gln polymorphisms were not associated with the development of HNSCC in Turkish population. In addition, the allele frequencies of polymorphisms were in line with other Turkish population results that were studied previously. However, compared to different populations, there were marked differences in allele frequencies.

Meng X, Wu X, Yuan Y
[Significances of COX-2, p21, Ki-67 expression and HPV infection in nasal inverted papilloma].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014; 28(23):1823-7 [PubMed] Related Publications
OBJECTIVE: To investigate the significance of expression of COX-2, p21, Ki67 and HPV in nasal inverted papilloma.
METHOD: Detecting COX-2, p21, Ki-67 in 30 cases of nasal inverted papilloma (NIP), 20 cases of nasal polyps (NP) and 10 cases of normal nasal mucosa (NM) by two step immunohistochemical method, and HPV virus by flow-through hybridization method.
RESULT: The positive expression rate of COX-2 and Ki-67 in NIP, NP and NM group was decreased in turn, COX-2 had significant difference in the groups(χ2 = 30.00, P< 0. 05); the positive expression rate of Ki-67 had significant differences between NIP and NM group (χ2 = 8. 533, P<0. 05). The expression of COX-2 in NIP tissues was positively correlate with that of Ki-67 by using Spearman rank correlation analysis (r=0.78, P<0.05). Expression of p21 were not observed in NIP group. The positive rate of HPV was 26. 67% in 30 cases of NIP, all of HPV16 type.
CONCLUSION: COX-2, Ki-67 and HPV infection have certain correlation with the occurrence of NIP. The occurrence of NIP has relationship with inflammatory reaction mediated by COX-2. Ki-67 can well reflect the proliferation activity of tumor cells, and can be used to measure the proliferation rate of nasal inverted papilloma. The COX-2 and Ki-67 have a synergistic role in the pathogenesis of NIP. p21 has no significant relationship with the incidence of NIP. HPV infection is related to the pathogenesis of NIP, but not as a;major factor in the pathogenesis of NIP.

Zhang J, Yang Y, Tang Y, et al.
[The quantification and significance of muscle segment homeobox gene Msx2, human topoisomerase II-α, HPV16 and VEGF in sinonasal inverted papilloma].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014; 28(23):1819-23 [PubMed] Related Publications
OBJECTIVE: To investigate the quantification and significance of Msx2, topoII-α; HPV16 and VEGF in sinonasal inverted papilloma(SNIP), to study the correlation among the four factors,and to discover the relationship between Msx2 and topoII-α in the process of SNIP malignant transfomation.
METHOD: Real-time quantitative Polymerase Chain Reaction (RT-qPCR) was used to detect the expression of Msx2, topoII-α, HPV16 and VEGF in 13 cases of sinonasal inverted papilloma (SNIP), 10 cases of sinonasal squamous cell carcinoma(NSCC) and 10 cases of inflammatory nasal polyp paraffin (INP)tissues. According to the pathology results SNIP were divided into mild dysplasia, moderate dysplasia and severe dysplasia. All the data were analysised by SPSS17. 0, P<0. 05 was refered to statistically significant difference.
RESULT: The mRNA level of Msx2, topoII-α, VEGF and HPV16 in SNIP, NSCC tissues were significantly higher than in the INP tissues (P<0. 05). The expression differences of Msx2, topoII-α, HPV16 and VEGF mRNA level in SNIP tissues which were divided into three groups according to their pathological results,were all statistically significantly different between any two of the three groups (P< 0. 05). Using Pearson correlation coefficient analysis,we found positive correlation between any two of the mRNA level of Msx2, topoII-α, VEGF and HPV16 (P<0. 05).
CONCLUSION: Msx2 and topoII-α may play an important role in the process of SNIP Malignant transformation,which may be new targets for gene therapy of SNIP and NSCC.

Shi C, Qin H, Ding C, et al.
[Association between BRAF V600E mutation and central lymph node metastasis in patients with papillary thyroid carcinoma].
Zhonghua Zhong Liu Za Zhi. 2015; 37(2):123-7 [PubMed] Related Publications
OBJECTIVE: To investigate the association of concomitant BRAFV600E mutation with central lymph node metastases in papillary thyroid carcinoma (PTC).
METHODS: The clinicopathological data of 126 PTC patients who underwent surgical treatment within a period of 2 years were retrospectively analyzed. The BRAF V600E gene mutation was detected by quantitative fluorescence PCR.
RESULTS: The BRAF mutation rate was 69.0% (87/126). The univariate analysis showed that BRAF mutation status was significantly associated with central lymph node metastasis (P<0.05), while the gender, multiple lesions, tumor size, extra-thyroidal invasion, Hashimoto's thyroiditis and tumor stage were not significantly associated with the BRAF mutation (P>0.05 for all). The multivariate analysis showed that only central lymph node metastasis was significantly correlated with BRAF mutation (P<0.05). When the diameter of tumor was ≤10 mm, BRAF mutation was statistically not significantly correlated to central lymph node metastasis (P>0.05). When the diameter of tumor was >10 mm, the central lymph node metastasis rate was significantly higher in patients with positive BRAF mutation than that in patients with a negative BRAF mutation (P<0.05).
CONCLUSIONS: The presence of BRAF mutation is an independent predictive factor for central lymph node metastasis. When PTC is with preoperative positive BRAF mutation, the cervical dissection should be routinely performed. The larger the tumor diameter is, the more important is the central lymph node dissection. There should be re-evaluated the necessity of preventative central lymph node dissection when the tumor diameter was ≤5 mm in patients with negative BRAF mutation.

Chernock RD, Hagemann IS
Molecular pathology of hereditary and sporadic medullary thyroid carcinomas.
Am J Clin Pathol. 2015; 143(6):768-77 [PubMed] Related Publications
OBJECTIVES: Medullary thyroid carcinoma (MTC) is a relatively uncommon type of thyroid malignancy, with unique histologic features and molecular pathology. It is important to recognize, because its management, which is in part driven by the genetic basis of this disease, is different from follicular-derived thyroid tumors. The aim of this article is to briefly review the histopathologic features of MTC and then explore its molecular pathology, including the role of molecular diagnostic testing and the use of targeted therapy for advanced disease.
METHODS: A review of published literature was performed.
RESULTS: A subset of MTC cases is hereditary and due to germline mutations in the RET tyrosine kinase receptor gene. Somatic mutations in either RET or RAS are also present in most sporadic tumors.
CONCLUSIONS: Molecular genetic testing is routinely performed to identify hereditary cases. In addition, understanding the molecular basis of both hereditary and sporadic MTC has led to the development of targeted therapy with tyrosine kinase inhibitors. Although additional data are needed, tumor mutation status may affect response to targeted therapy. Therefore, it is possible that genetic testing of tumor tissue to predict treatment response, as is currently done for other cancer types, may come into practice in the future.

Peng XE, Chen HF, Hu ZJ, Shi XS
Independent and combined effects of environmental factors and CYP2C19 polymorphisms on the risk of esophageal squamous cell carcinoma in Fujian Province of China.
BMC Med Genet. 2015; 16:15 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The purpose of this study was to explore the effects of CYP2C19 gene polymorphisms and various environmental factors and their interactions on the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese Han population.
METHODS: A 1:2 frequency-matched case control study of 285 patients and 570 controls was conducted from June 2010 to May 2011 in AnXi of Fujian province, China. Environmental factors were investigated using a self-administered questionnaire and genotypes were determined using polymerase chain reaction restriction fragment length polymorphism based methods. Unconditional logistic regression models were used for statistical evaluation.
RESULTS: Current or former smoking, consumption of pickled vegetables or hot beverages/food, having a first degree relative with ESCC and history of reflux esophagitis were significantly associated with increased ESCC risk, whereas tea drinking and consumption of fresh vegetables and fruits were significantly associated with decreased risk. The CYP2C19*2 GA/AA genotype was significantly more prevalent in ESCC patients and individuals with at least one copy of the CYP2C19*2 A allele had a 3.19-fold increased risk (adjusted 95% confidence interval (CI): 2.21-4.61, P < 0.001) of ESCC compared with those without this allele. We found no significant associations between CYP2C19*3 genotypes and ESCC. The Cyp2C19*2 polymorphism appeared to have a multiplicative joint effect with tea drinking and hot beverage/food consumption (gene-tea drinking: P(interaction) = 0.042; hot beverage/food consumption: P(interaction) = 6.98 × 10(-6)) and an additive joint effect with pickled vegetable consumption (interaction contrast ratio = 1.96, 95% CI: 0.12-3.80).
CONCLUSIONS: Our findings suggest that the CYP2C19*2 polymorphism plays an important role in the development of ESCC in the Chinese population, modified by tea drinking and consumption of pickled vegetables or hot beverages/food. Further studies are warranted to confirm our results.

Zhang X, Xu Y, He C, et al.
Elevated expression of CCAT2 is associated with poor prognosis in esophageal squamous cell carcinoma.
J Surg Oncol. 2015; 111(7):834-9 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: CCAT2, a novel long non-coding RNAs (lncRNAs), is found to promote the metastasis and invasion of colon, lung, and breast cancers. This study aimed to investigate the level of CCAT2 in esophageal squamous cell carcinoma (ESCC) and to elucidate its clinical significance.
METHODS: The expression level of CCAT2 and the status of MYC amplification were examined in 229 ESCC samples using quantitative real- time PCR.
RESULTS: CCAT2 was upregulated in ESCC tissues, especially in cases with lymph node metastasis (LNM), advanced TNM stages, and MYC amplification. Furthermore, the level of CCAT2 was positively correlated with TNM stages, LNM, and the number of positive lymph nodes. High CCAT2 expression and MYC amplification were significantly associated with TNM stages and LNM. Survival analyses revealed that high CCAT2 expression and MYC amplification were significantly associated with poorer overall survival in ESCC patients. Furthermore, patients with high CCAT2 expression and MYC amplification had a 2.199-fold increased risk of death compared with those with low CCAT2 expression and MYC non-amplification.
CONCLUSIONS: Our study provides the first evidence associating CCAT2 expression and poor survival in ESCC. CCAT2 may be a prognostic biomarker and therapeutic target for ESCC.

Lopes-Aguiar L, Visacri MB, Nourani CM, et al.
Do genetic polymorphisms modulate response rate and toxicity of Cisplatin associated with radiotherapy in laryngeal squamous cell carcinoma?: a case report.
Medicine (Baltimore). 2015; 94(16):e578 [PubMed] Related Publications
UNLABELLED: Cisplatin (CDDP) plus radiotherapy (RT) has been used to treat advanced laryngeal squamous cell carcinoma (LSCC) patients. Single nucleotide polymorphisms (SNPs) may be responsible for differences in chemo/radiosensitivity and side effects in those patients. We reported an advanced LSCC patient, who obtained durable complete response and unexpected pronounced toxicity during CDDP and RT, possibly due to SNPs in genes that modulate the effects of this therapeutic modality.
CASE PRESENTATION: A 30-year-old man with advanced LSCC obtained durable complete response and severe alopecia and pancytopenia after standard and reduced doses of CDDP and RT. Analyses of SNPs revealed that the patient presented GSTT1 deletion, variant MSH3 1045ThrThr, wild GSTP1 105IleIle, and wild BAX -248GG genotypes, which were previously described in association with abnormal detoxification, DNA repair, and damaged cell apoptosis, respectively. Seven other advanced LSCC patients with GSTT1 gene, MSH3 AlaAla or AlaThr, GSTP1 IleVal or ValVal, and BAX GA or AA genotypes served as controls of the study. Only 1 control presented complete response; the other 6 controls obtained partial response of short duration. Four and 3 controls presented grade 1 or 2 and grade 3 anemia or leukopenia during treatment, respectively. The CDDP level in urine collected after CDDP infusion in the reported patient was lower than the median value obtained in controls, suggesting a higher amount of intracellular CDDP in the reported case.The data suggest, for the first time, that inherited abnormalities in intracellular detoxification of CDDP, DNA repair of lesions induced by CDDP and RT, and damaged cell apoptosis may alter treatment response and toxicity in LSCC, but should be confirmed by large pharmacogenomic studies.

Starska K, Bryś M, Forma E, et al.
The effect of metallothionein 2A core promoter region single-nucleotide polymorphism on accumulation of toxic metals in sinonasal inverted papilloma tissues.
Toxicol Appl Pharmacol. 2015; 285(3):187-97 [PubMed] Related Publications
Metallothioneins (MTs) are intracellular thiol-rich heavy metal-binding proteins which join trace metal ions protecting cells against heavy metal toxicity and regulate metal distribution and donation to various enzymes and transcription factors. The goal of this study was to identify the -5 A/G (rs28366003) single-nucleotide polymorphism (SNP) in the core promoter region of the MT2A gene, and to investigate its effect on allele-specific gene expression and Cd, Zn, Cu and Ni content in sinonasal inverted papilloma tissue (IP), with non-cancerous sinonasal mucosa (NCM) as a control. The MT2A promoter region -5 A/G SNP was identified by restriction fragment length polymorphism using 117 IP and 132 NCM. MT2A gene analysis was performed by quantitative real-time PCR. Metal levels were analyzed by flame atomic absorption spectrometry. The frequency of A allele carriage was 99.2% and 100% in IP and NCM, respectively. The G allele carriage was detected in 23.9% of IP and in 12.1% of the NCM samples. As a result, a significant association of -5 A/G SNP in MT2A gene with mRNA expression in both groups was determined. A significant association was identified between the -5 A/G SNP in the MT2A gene with mRNA expression in both groups. A highly significant association was detected between the rs28366003 genotype and Cd and Zn content in IP. Furthermore, significant differences were identified between A/A and A/G genotype with regard to the type of metal contaminant. The Spearman rank correlation results showed the MT2A gene expression and both Cd and Cu levels were negatively correlated. The results obtained in this study suggest that the -5 A/G SNP in the MT2A gene may have an effect on allele-specific gene expression and toxic metal accumulation in sinonasal inverted papilloma.

Zhou Z, Zhang L, Xie B, et al.
FOXC2 promotes chemoresistance in nasopharyngeal carcinomas via induction of epithelial mesenchymal transition.
Cancer Lett. 2015; 363(2):137-45 [PubMed] Related Publications
Paclitaxel (Taxol) is currently used as the front-line chemotherapeutic drug for many types of human cancers. However, the emergence of drug resistance has been a major obstacle to the effective treatment of cancers in clinical settings. The transcription factor Forkhead box protein C2 (FOXC2) was recently demonstrated to activate the epithelial-mesenchymal transition (EMT). In this article, we present a novel role of FOXC2 in regulating chemoresistance of nasopharyngeal carcinoma (NPC) through the EMT. Using an EMT PCR array based on the screening of 84 genes, the expression of FOXC2 was notably upregulated in paclitaxel-resistant NPC cells (CNE2/t). We observed that the paclitaxel-resistant cells exhibited characteristic EMT phenotypes. The silencing of FOXC2 expression in the resistant cells can reverse the EMT molecular markers and chemoresistant phenotypes, such as cellular morphology, proliferation and anoikis. In an NPC xenograft mouse model, the downregulation of FOXC2 expression in the resistant NPC cells increased their sensitivity to paclitaxel treatment, resulting in reduced tumor growth. Taken together, our results suggest that FOXC2-mediated EMT may be an alternative mechanism through which cancer cells can initiate and maintain drug resistance. Thus, targeting FOXC2 may provide a novel strategy for overcoming chemoresistance in NPC therapy.

Ren Y, Zhang S, Li X, et al.
[Combined application the siRNA target for Hif-lα and Survivin gene to human NPC CNE-2 cell and its effects on the proliferation and cycle of this cell].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014; 28(24):1975-8 [PubMed] Related Publications
OBJECTIVE: To study the combined transfection of the siRNA target for Hif-lα and Survivin gene to human NPC CNE-2 cell and its effects on the proliferation and cycle of this cell.
METHOD: Combined transfection of the siRNA target for Hif-lα and Survivin gene to human NPC CNE-2 cell, these plasmids were respectively transfected into the same cells. Cell proliferation was detected with MTT assay. The inhibitory effects on target genes were evaluated with RT-PCR and Western Blot at the levels of mRNA and protein, respectively.
RESULT: MTT showed that CNE-2 cell proliferation in multi-gene plasmid group was more significantly inhibited than a single gene. The expression of mRNA and protein of two different genes were both decreased in HS group, and the interference effect of multiple genes was better than the single-gene(P<0.01).
CONCLUSION: HS group could restrain cell proliferation and interference the mRNA and protein expression in nasopharyngeal carcinoma CNE-2 cell, which was better than the other groups.

Xu YF, Mao YP, Li YQ, et al.
MicroRNA-93 promotes cell growth and invasion in nasopharyngeal carcinoma by targeting disabled homolog-2.
Cancer Lett. 2015; 363(2):146-55 [PubMed] Related Publications
Dysregulation of microRNAs (miRNAs) has been demonstrated to contribute to malignant progression in nasopharyngeal carcinoma (NPC). We previously reported that miR-93 was significantly upregulated in NPC based on a microarray analysis. However, the potential role and mechanism of action of miR-93 in the initiation and progression of NPC remain largely unknown. Quantitative RT-PCR demonstrated that miR-93 was significantly upregulated in NPC cell lines and clinical specimens. The MTT assay, colony formation assay, anchorage-independent growth, and Transwell migration and invasion assays showed that depletion of miR-93 inhibited NPC cell growth, invasion and migration in vitro and suppressed tumor growth in vivo. Disabled homolog-2 (Dab2) was verified as a miR-93 target gene using Luciferase reporter assays, quantitative RT-PCR and Western blotting and was involved in miR-93-regulated NPC cell growth, invasion and migration. These results indicated that miR-93 plays an important role in the initiation and progression of NPC by targeting Dab2 and the miR-93/Dab2 pathway may contribute to the development of novel therapeutic strategies for NPC in the future.

Chunli W, Jiajie H, Lifei W, et al.
[IGHMBP2 overexpression promotes cell migration and invasion in esophageal squamous carcinoma].
Yi Chuan. 2015; 37(4):360-6 [PubMed] Related Publications
Immunoglobulin mu binding protein 2 (IGHMBP2) is located in 11q13.2, which is frequently amplified in esophageal squamous cell carcinoma (ESCC). IGHMBP2 encodes a helicase involved in DNA replication and repair. IGHMBP2 protein also regulates gene transcription. The present study aims to explore the amplification of IGHMBP2 and its potential role in ESCC. A further analysis of our previously reported array-CGH data showed that IGHMBP2 was amplified in 28.9% of primary ESCC tumors. Fluorescence in situ hybridization (FISH) and Western blot showed that IGHMBP2 was amplified and overexpressed in KYSE30, KYSE180, KYSE510 and KYSE150 esophageal cancer cell lines. Transwell assays demonstrated that knockdown of IGHMBP2 in KYSE30 and KYSE150 inhibited cell invasion and migration, and increased the expression levels of E-cadherin. When rescue plasmids expressing IGHMBP2 were introduced, the abilities of cell invasion and migration were restored. These data suggest that IGHMBP2 overexpression may promote invasion and migration of ESCC cells through down-regulation of E-cadherin.

Fisher OM, Levert-Mignon AJ, Lord SJ, et al.
MIC-1/GDF15 in Barrett's oesophagus and oesophageal adenocarcinoma.
Br J Cancer. 2015; 112(8):1384-91 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Biomarkers are needed to improve current diagnosis and surveillance strategies for patients with Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC). Macrophage inhibitory cytokine 1/growth differentiation factor 15 (MIC-1/GDF15) tissue and plasma levels have been shown to predict disease progression in other cancer types and was therefore evaluated in BO/OAC.
METHODS: One hundred thirty-eight patients were studied: 45 normal oesophagus (NE), 37 BO, 16 BO with low-grade dysplasia (LGD) and 40 OAC.
RESULTS: Median tissue expression of MIC-1/GDF15 mRNA was ⩾25-fold higher in BO and LGD compared to NE (P<0.001); two-fold higher in OAC vs BO (P=0.039); and 47-fold higher in OAC vs NE (P<0.001). Relative MIC-1/GDF15 tissue expression >720 discriminated between the presence of either OAC or LGD vs NE with 94% sensitivity and 71% specificity (ROC AUC 0.86, 95% CI 0.73-0.96; P<0.001). Macrophage inhibitory cytokine 1/growth differentiation factor 15 plasma values were also elevated in patients with OAC vs NE (P<0.001) or BO (P=0.015).High MIC-1/GDF15 plasma levels (⩾1140 pg ml(-1)) were an independent predictor of poor survival for patients with OAC (HR 3.87, 95% CI 1.01-14.75; P=0.047).
CONCLUSIONS: Plasma and tissue levels of MIC-1/GDF15 are significantly elevated in patients with BO, LGD and OAC. Plasma MIC-1/GDF15 may have value in diagnosis and monitoring of Barrett's disease.

Fan S, Chen WX, Lv XB, et al.
miR-483-5p determines mitochondrial fission and cisplatin sensitivity in tongue squamous cell carcinoma by targeting FIS1.
Cancer Lett. 2015; 362(2):183-91 [PubMed] Related Publications
Mitochondria play an important role in the initiation of apoptosis. However, whether cisplatin can induce apoptosis by initiating a mitochondrial fission pathway and the mechanism underlying this effect remain poorly understood. In this study, we show that the mitochondrial fission protein FIS1 is upregulated upon cisplatin treatment in tongue squamous cell carcinoma (TSCC) cells. FIS1 knockdown can attenuate mitochondrial fission and cisplatin sensitivity. We found that FIS1 is a direct target of miR-483-5p and that miR-483-5p can inhibit mitochondrial fission and cisplatin sensitivity in vitro and in vivo. Furthermore, we found that miR-483-5p and FIS1 are significantly associated with cisplatin sensitivity and with overall survival in patients with TSCC in a retrospective analysis of multiple centers. This study revealed that a novel mitochondrial fission pathway composed of miR-483-5p and FIS1 regulates cisplatin sensitivity. The modulation of miR-483-5p and FIS1 levels may provide a new approach for increasing cisplatin sensitivity.

Zhang L, Zhou Y, Cheng C, et al.
Genomic analyses reveal mutational signatures and frequently altered genes in esophageal squamous cell carcinoma.
Am J Hum Genet. 2015; 96(4):597-611 [PubMed] Free Access to Full Article Related Publications
Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets.

Delahaye-Sourdeix M, Anantharaman D, Timofeeva MN, et al.
A rare truncating BRCA2 variant and genetic susceptibility to upper aerodigestive tract cancer.
J Natl Cancer Inst. 2015; 107(5) [PubMed] Related Publications
Deleterious BRCA2 genetic variants markedly increase risk of developing breast cancer. A rare truncating BRCA2 genetic variant, rs11571833 (K3326X), has been associated with a 2.5-fold risk of lung squamous cell carcinoma but only a modest 26% increase in breast cancer risk. We analyzed the association between BRCA2 SNP rs11571833 and upper aerodigestive tract (UADT) cancer risk with multivariable unconditional logistic regression adjusted by sex and combinations of study and country for 5942 UADT squamous cell carcinoma case patients and 8086 control patients from nine different studies. All statistical tests were two-sided. rs11571833 was associated with UADT cancers (odds ratio = 2.53, 95% confidence interval = 1.89 to 3.38, P = 3x10(-10)) and was present in European, Latin American, and Indian populations but extremely rare in Japanese populations. The association appeared more apparent in smokers (current or former) compared with never smokers (P het = .026). A robust association between a truncating BRCA2 variant and UADT cancer risk suggests that treatment strategies orientated towards BRCA2 mutations may warrant further investigation in UADT tumors.

Song Y, Wang Y, Xu L, et al.
A genetic variant in CHRNB3-CHRNA6 increases risk of esophageal squamous cell carcinoma in Chinese populations.
Carcinogenesis. 2015; 36(5):538-42 [PubMed] Related Publications
Nicotinic acetylcholine receptors are important regulators of smoking behavior and tobacco carcinogenesis. We studied the association of the CHRNB3-A6 variant rs13280604 in relation to esophageal squamous cell carcinoma (ESCC) in Chinese populations. Two independent case-control studies were conducted. The first case-control study, consisted of 866 ESCC patients and 1621 healthy controls from Northern China, and the second case-control study consisted of 853 ESCC patients and 860 unrelated controls from Southern China. A logistic regression model was used to evaluate the associations of rs13280604 with cancer risk. We found that Rs13280604 GG/AG genotypes were significantly associated with increased risk for ESCC in both case-control studies from Northern [odds ratio (OR), 1.42, 95% confidence interval (CI), 1.19-1.70, P = 1.1×10(-4)], Southern China (OR, 1.56, 95% CI, 1.26-1.93, P = 5.2×10(-5)), and the combined population of both studies (OR, 1.44, 95% CI, 1.26-1.65, P = 8.7×10(-8)), respectively. Our results suggest that this CHRNB3-A6 variant confers susceptibility to ESCC risk. However, future larger studies are needed to validate our finding.

Nagarajah J, Ho AL, Tuttle RM, et al.
Correlation of BRAFV600E Mutation and Glucose Metabolism in Thyroid Cancer Patients: An ¹⁸F-FDG PET Study.
J Nucl Med. 2015; 56(5):662-7 [PubMed] Related Publications
UNLABELLED: There is significant interest in a better understanding of the genetic underpinnings of the increased glucose metabolic rates of cancer cells. Thyroid cancer demonstrates a broad variability of (18)F-FDG uptake as well as several well-characterized oncogenic mutations. In this study, we evaluated the differences in glucose metabolism of the BRAF(V600E) mutation versus BRAF wild-type (BRAF-WT) in patients with metastatic differentiated thyroid cancer (DTC) and poorly differentiated thyroid cancer (PDTC).
METHODS: Forty-eight DTC and 34 PDTC patients who underwent (18)F-FDG PET/CT for tumor staging were identified from a database search. All patients were tested for the BRAF(V600E) mutation and assigned to 1 of 2 groups: BRAF(V600E) mutated and BRAF-WT. (18)F-FDG uptake of tumor tissue was quantified by maximum standardized uptake value (SUVmax) of the hottest malignant lesion in 6 prespecified body regions (thyroid bed, lymph nodes, lung, bone, soft tissue, and other). When there were multiple lesions in 1 of the prespecified body regions, only the 1 with the highest (18)F-FDG uptake was analyzed.
RESULTS: In the DTC cohort, 24 tumors harbored a BRAF(V600E) mutation, whereas 24 tumors were BRAF-WT. (18)F-FDG uptake of BRAF(V600E)-positive lesions (median SUVmax, 6.3; n = 53) was significantly higher than that of BRAF-WT lesions (n = 39; median SUVmax, 4.7; P = 0.019). In the PDTC group, only 5 tumors were BRAF(V600E)-positive, and their (18)F-FDG uptake was not significantly different from the BRAF-WT tumors. There was also no significant difference between the SUVmax of all DTCs and PDTCs, regardless of BRAF mutational status (P = 0.90).
CONCLUSION: These data suggest that BRAF(V600E)-mutated DTCs are significantly more (18)F-FDG-avid than BRAF-WT tumors. The effect of BRAF(V600E) on tumor glucose metabolism in PDTC needs further study in larger groups of patients.

Slaby O, Srovnal J, Radova L, et al.
Dynamic changes in microRNA expression profiles reflect progression of Barrett's esophagus to esophageal adenocarcinoma.
Carcinogenesis. 2015; 36(5):521-7 [PubMed] Related Publications
Esophageal adenocarcinoma (EAC) is highly aggressive malignancy that frequently develops from Barrett's esophagus (BE), a premalignant pathologic change occurring in the lower end of the esophagus. MicroRNAs (miRNAs) are small, non-coding RNAs that function as posttranscriptional regulators of gene expression and were repeatedly proved to play key roles in pathogenesis of BE as well as EAC. In our study, we used Affymetrix GeneChip miRNA arrays to obtain miRNA expression profiles in total of 119 tissue samples [24 normal esophageal mucosa (EM), 60 BE and 35 EAC]. We identified a number of miRNAs, that showed altered expression progressively in sequence EM, BE and EAC, including for instance miR-21, miR-25, miR-194 and miR-196a with increasing levels (P < 0.0015) and miR-203, miR-205, miR-210 and miR-378 with decreasing levels (P < 0.0001). The subsequent analysis revealed four diagnostic miRNA signatures enabling to distinguish EM and BE [12 miRNAs, area under curve (AUC) = 0.971], EM and EAC (13 miRNAs, AUC = 1.0), BE without and BE with dysplasia (21 miRNAs, AUC = 0.856) and BE without dysplastic changes and BE with dysplasia together with EAC (2 miRNAs, AUC = 0.886). We suggest that miRNA expression profiling expands current knowledge in molecular pathology of Barrett's-based carcinogenesis and enables identification of molecular biomarkers for early detection of BE dysplasia and progression to EAC.

Shi Q, Ibrahim A, Herbert K, et al.
Detection of BRAF mutations on direct smears of thyroid fine-needle aspirates through cell transfer technique.
Am J Clin Pathol. 2015; 143(4):500-4 [PubMed] Related Publications
OBJECTIVES: To determine the utility of the cell transfer technique (CTT) for BRAF molecular testing on thyroid fine-needle aspiration (FNA) specimens.
METHODS: Polymerase chain reaction (PCR)-based BRAF molecular testing was performed on tissues obtained through CTT from both air-dried and ethanol-fixed direct smears of thyroid FNA specimens and then compared with the corresponding thyroidectomy formalin-fixed, paraffin-embedded (FFPE) tissues on 30 cases.
RESULTS: BRAF testing was successfully performed on 29 of 30 air-dried CTT, 27 of 30 ethanol-fixed CTT, and 27 of 30 FFPE tissues. The results exhibited 11, 13, and 13 BRAF mutations and 18, 14, and 14 wild types for the air-dried CTT, the ethanol-fixed CTT, and the FFPE tissues, respectively. The concordance rate was 96% between air-dried and ethanol-fixed CTT tissues, 88% between air-dried CTT and FFPE tissues, and 92% between ethanol-fixed CTT and FFPE tissues.
CONCLUSIONS: PCR-based BRAF mutational testing can be reliably performed on the direct smears of the thyroid FNA specimens through the application of CTT.

Yu C, Guo J, Liu Y, et al.
Oral squamous cancer cell exploits hnRNP A1 to regulate cell cycle and proliferation.
J Cell Physiol. 2015; 230(9):2252-61 [PubMed] Related Publications
Oral squamous cell carcinoma (OSCC) is a common human malignant tumor with high mortality. So far, the molecular pathogenesis of OSCC remains largely unclear. Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is an important multi-function splicing factor and closely related to tumorigenesis. hnRNP A1 is overexpressed in various tumors, and promotes aerobic glycolysis and elongation of telomere, but the function of hnRNP A1 in cell cycle and proliferation remains unclear. We found that hnRNP A1 was overexpressed in OSCC tissues, and was required for the growth of OSCC cells. Moreover, hnRNP A1 was highly expressed in the G2/M cell cycle phase. Knockdown of hnRNP A1 induced G2/M arrest. DNA microarray assay result showed that hnRNP A1 regulated the expression of a number of target genes associated with G2/M phase. Moreover, hnRNP A1 controlled the alternative splicing of CDK2 exon 5. These findings suggested that hnRNP A1 plays key roles in the regulation of cell cycle progression and pathogenesis of OSCC.

Veit JA, Scheckenbach K, Schuler PJ, et al.
MicroRNA expression in differentially metastasizing tumors of the head and neck: adenoid cystic versus squamous cell carcinoma.
Anticancer Res. 2015; 35(3):1271-7 [PubMed] Related Publications
BACKGROUND/AIM: Head and neck adenoid cystic carcinoma (HNACC) is a rare malignancy of the salivary glands with a tendency to metastasize in lung or liver without lymph node involvement, whereas squamous cell carcinoma (HNSCC) preferentially metastasizes to locoregional lymph nodes. The expression patterns of microRNA, a class of small non-coding RNA transcripts, involved in gene regulation and various developmental processes, could be of influence during the metastatic process. The aim of the present study was to compare mircoRNA expression patterns of HNACC and HNSCC.
MATERIALS AND METHODS: In a total of 21 tissue samples, a genome-wide screening for microRNAs was performed. A microRNA array platform was used for the identification of target microRNA.
RESULTS: Five microRNAs, hsa-MiR-214, hsa-MiR-125a-5p, hsa-MiR-574-3p, hsa-MiR-199a-3p/199b-3p and hsa-miR-199a-5p were identified to be over-expressed in HNACC compared to HNSCC, whereas hsa-MiR-452 showed a lower expression level.
CONCLUSION: Our data showed significantly different expression patterns of mircoRNA in HNACC and HNSCC supporting the theory of tumor-specific expression and giving hints for different clinical behavior.

Guo XF, Wang J, Lei XF, et al.
XPD Lys751Gln polymorphisms and the risk of esophageal cancer: an updated meta-analysis.
Intern Med. 2015; 54(3):251-9 [PubMed] Related Publications
OBJECTIVE: Published data regarding the association between xeroderma pigmentosum group D XPD Lys751Gln polymorphisms and esophageal cancer (EC) cancer remain controversial. The present meta-analysis aimed to obtain a more precise estimation of the relationship between XPD Lys751Gln polymorphisms and the risk of EC.
METHODS: All eligible case-control studies of Lys751Gln polymorphisms and susceptibility to EC were selected from PubMed, Web of Science and CNKI up to October 2013. The data were extracted, and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.
RESULTS: A total of 21 case-control studies from 19 reports were assessed in this meta-analysis, including 6,581 cases and 8,251 controls. There was a significant association between the XPD Lys751Gln polymorphism and the risk of esophageal cancer in the overall population (Dominant model: OR=1.30, 95%CI: 1.07-1.57, p<0.05; Lys/Gln vs. Gln/Gln: OR=1.20, 95%CI: 1.05-137, p<0.05; Gln/Gln vs. Lys/Lys: OR=1.76, 95%CI: 1.08-2.85, p=0.02; Recessive model: OR=1.48, 95%CI: 1.06-2.07, p=0.02). Similar results were found when stratified according to the cancer type, ethnicity and control source. However, no associations were found among smokers or drinkers.
CONCLUSION: The results of this meta-analysis suggest that XPD Lys751Gln polymorphisms contribute to susceptibility to EC.

Wei WJ, Lu ZW, Wang Y, et al.
Clinical significance of papillary thyroid cancer risk loci identified by genome-wide association studies.
Cancer Genet. 2015; 208(3):68-75 [PubMed] Related Publications
Four single nucleotide polymorphisms (SNPs) have been reported to be associated with thyroid cancer risk in two genome-wide association studies (GWASs) and were validated in a Chinese population. Because of a lack of further clinical and functional evidence, the clinical significances of these SNPs remain unknown. Four GWAS-identified SNPs of papillary thyroid cancer (PTC), rs965513, rs944289, rs966423 and rs2439302, were genotyped in a case-control study of 838 patients with PTC and 501 patients with benign thyroid tumor (BTT) from the Chinese Han population. The associations between these SNPs, clinicopathologic features, and the outcome of the PTC patients were examined. The CT and CT + TT genotypes of rs966423 were more common in PTC patients with extrathyroidal extension and more advanced T stage. The TC and TC + CC genotypes and the C allele of rs944289 were significantly less frequent in patients with multifocal disease. No correlation was observed between GWAS-identified SNPs and disease persistence of PTC after a short-term follow-up. Significantly different allele distributions between the PTC and BTT groups were observed for all four selected SNPs. Individuals with more than five risk alleles were 8.84-fold (95% CI 3.23-24.17) more likely to suffer from PTC compared with those with zero or 1 risk allele. GWAS-identified SNPs affect the individual predisposition to PTC without interacting with existing Hashimoto thyroiditis and BTT lesions. GWAS-identified SNPs were associated with certain clinicopathologic features of PTC, and may contribute to identifying PTC patients with different clinical patterns. Large prospective studies are required to further evaluate the diagnostic and prognostic power of these genetic markers.

Seven D, Yavuz E, Kilic E, et al.
DLEC1 is not silenced solely by promoter methylation in head and neck squamous cell carcinoma.
Gene. 2015; 563(1):83-6 [PubMed] Related Publications
Different types of genetic and epigenetic changes are associated with HNSCC. The molecular mechanisms of HNSCC carcinogenesis are still undergoing intensive investigation. The Deleted in lung and esophageal cancer 1 (DLEC1) gene is frequently silenced by methylation in various kinds of cancer. However, there is no data in the literature investigating the DLEC1 gene in the HNSCC. Tumor tissues from 97 patients were analyzed by real-time quantitative RT-PCR and DLEC1 expression levels were correlated with the methylation of the DLEC1 gene promoter. A statistically significant down-regulation was observed in tumors compared to non-cancerous tissue samples (p = 0.00). However, this down-regulation was not directly associated with hypermethylation of the promoter (p ≥ 0.05). Our results indicate that the DLEC1 gene may play an important role in the development of HNSCC. However, its down-regulation is not associated with the clinicopathological parameters and is not solely under the control of promoter methylation.

Zeki S, Fitzgerald RC
The use of molecular markers in predicting dysplasia and guiding treatment.
Best Pract Res Clin Gastroenterol. 2015; 29(1):113-24 [PubMed] Related Publications
The ability to stratify patients based on the risk of progression to oesophageal adenocarcinoma would provide benefit to patients as well as deliver a more cost effective surveillance programme. Current practice is to survey all patients with Barrett's oesophagus (BO) and use histological diagnoses to guide further management. However, reliance on histology alone has its drawbacks. We are currently unable to reliably stratify the risk of progression of patients with non-dysplastic BO based on any particular histological feature. There is also considerable variability in histological interpretation. An obvious recourse has been to rely on identifying molecular features possibly as an adjunct to histology, to better diagnose and stratify patients. To this end, p53 immunohistochemistry can be used as a useful adjunct to risk stratify and clarify histological grades, particularly low-grade dysplasia. Other markers of progression, although not yet in a clinically applicable format, are promising. Measurements of promoter methylation and also genomic instability such as loss of heterozygosity and copy number alterations show promise especially as high throughput genetic technologies reach maturity. The enduring hope is that these molecular biomarkers will make the transition to clinical applicability either in the direct endoscopic setting or even using non-endoscopic methods.

Jiang Y, Wang P, Yu Y
[Relationship between the major histocompatibility complex class I chain-related gene A expression and clinicopathologic features in laryngeal squamous carcinoma].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014; 28(21):1694-696 [PubMed] Related Publications
OBJECTIVE: To investigate the expression of major histocompatibility complex class I chain-related gene A (MICA) in laryngeal squamous cell carcinoma(LSCC), and its clinical significance.
METHOD: Immunohistochemistry and RT-PCR were used to detect the expression of the MICA in LSCC and normal tissue samples. The relationship between the expression of MICA and the clinicopathologic features features were was analyzed.
RESULT: Compared to the expression of MICA in normal tissues samples, the expression of MICA in LSCC tissue was significantly increased (P < 0.01). MICA expression level in carcinoma tissue was closely related to the tumor-differentiation degree and TNM staging.
CONCLUSION: Our study suggests that MICA may play an important role in the invasion and metastasis of LSCC, and could be a potential tumor maker for LSCC.

Chen X, Yu Z, Gao Y, et al.
[Meta-analysis of association between MMP-1-1607 polymorphism and head and neck cancer risk in asia population].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014; 28(21):1679-84 [PubMed] Related Publications
OBJECTIVE: To analyze and explore the association between the 1607(1G/2G) single nucleotide polymorphism (SNP) in promoter of matrix metalloproteinase-1 (MMP-1) gene and susceptibility of head and neck cancer (HNC) by Meta-analysis.
METHOD: By the end of January 2014, the published literatures were collected for the case-control studies evaluating the relationship between HNC and -1607 SNP of MMP-1 gene from English and Chinese literature databases according to the inclusion and exclusion criteria. Then the meta-analysis, the heterogeneity, bias and sensitivity of the results of the eligible literatures were conducted by Stata 10. 0.
RESULT: A total of 9 studies including 2049 patients with HNC and 2158 controls were extracted for systematic review on the association of MMP-1 (-1607) 1G/2G SNP with the risk of HNC. Meta-analysis which based on random effects model showed that MMP-1 (-1607) 1G/2G SNP can significantly increase the risk of HNC[1G2G + 2G2G vs. 1G1G: OR = 1.45, 95% CI 1.25-1.68, P < 0.01; 2G2G vs. 1G1G + 1G2G:OR = 1.77, 95% CI 1.37-2.30, P < 0.01; 2G vs. 1G: OR = 1.52, 95% CI 1.26-1.85, P < 0.01; 2G2G vs. 1G1G: OR = 2.06, 95% CI 1.41-3.01, P < 0.01).
CONCLUSION: MMP-1 (-1607) 1G/2G SNP has close relationship with HNC susceptibility, people who with 2G2G genotype carriers are susceptible to HNC.

Recurring Structural Abnormalities

Selected list of common recurrent structural abnormalities

Abnormality Type Gene(s)
del(13q) in Head and Neck CancersDeletion

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.

del(13q) in Head and Neck Cancers

Maestro R, Piccinin S, Doglioni C, et al.
Chromosome 13q deletion mapping in head and neck squamous cell carcinomas: identification of two distinct regions of preferential loss.
Cancer Res. 1996; 56(5):1146-50 [PubMed] Related Publications
Heal and neck squamous cell carcinomas show frequent cytogenetic alterations involving the long arm of chromosome 13. To define the extent of 13q deletions and to identify the minimal areas of chromosome loss, 48 primary squamous cell carcinomas of the head and neck were analyzed for loss of heterozygosity using 11 different polymorphic loci. About 67% of the tumors displayed loss of genetic material at 13q. Most of the cases showed loss of the entire long arm of the chromosome. However, the presence of partial deletions in 10 cases provided evidence of the existence of two preferential sites of chromosome loss at 13q32-ter and 13q14.2-q14.3. The colocalization of the 13q14 minimal region of deletion with the retinoblastoma (RB) gene, which has been proposed as an oncosuppressor in diverse tumor types, prompted us to verify the involvement of this gene in the development of head and neck cancer. No significant variation in RB protein or RB mRNA expression was detected, thus excluding a role for such a gene in the genesis of this type of tumor. Taken together, our data suggest the existence of two new tumor suppressor genes (one close to and one distal to RB), which play a role in the development and/or progression of head and neck squamous cell carcinomas.

Gupta VK, Schmidt AP, Pashia ME, et al.
Multiple regions of deletion on chromosome arm 13q in head-and-neck squamous-cell carcinoma.
Int J Cancer. 1999; 84(5):453-7 [PubMed] Related Publications
Several lines of evidence suggest that the progression of head-and-neck squamous-cell carcinoma (HNSCC) involves inactivation of at least one and possibly several tumor-suppressor genes on the long arm of chromosome 13. The fact that neither Rb1 nor BRCA2 appears to be inactivated in the majority of head-and-neck cancers suggests that novel tumor-suppressor genes are involved. We have used microsatellite repeat polymorphisms and PCR to detect several distinct minimal regions of deletion on 13q in supraglottic and oral squamous-cell carcinomas. One region maps to 13q34, the second to 13q14.3 and a potential third region, not reported in previous studies, maps to 13q12.1. Overall, 69% of the 145 tumors examined demonstrated allelic loss at one or more loci on 13q. We investigated whether a novel suppressor candidate mapping to 13q14. 3-q21, leukemia-associated gene 1, might also be involved in the progression of squamous-cell carcinomas. Multiplexed PCR revealed homozygous deletion of leu1 in one oral cavity tumor. This suggests that this gene or one nearby may be the actual target of deletions in this region of the chromosome arm.

Sanchez-Cespedes M, Okami K, Cairns P, Sidransky D
Molecular analysis of the candidate tumor suppressor gene ING1 in human head and neck tumors with 13q deletions.
Genes Chromosomes Cancer. 2000; 27(3):319-22 [PubMed] Related Publications
The candidate tumor-suppressor gene ING1 encodes p33(ING1), a nuclear protein which physically interacts with TP53. It has been shown that p33(ING1) acts in the same biochemical pathway as TP53, leading to cell growth inhibition. Interestingly, a rearrangement of the ING1 gene was found in a neuroblastoma cell line, supporting its involvement in tumor development. Because ING1 resides on the long arm of chromosome 13 (13q34) (a region frequently deleted in many tumor types), we sought to characterize its role in head and neck squamous-cell carcinoma (HNSCC). We first analyzed 44 primary tumors for loss of heterozygosity (LOH) at 13q, using four widely spaced microsatellite markers (13q14, 13q14.3-q22, 13q22, and 13q34). Twenty (48%) of the tumor samples showed LOH in all of the informative markers tested, including D13S1315 at 13q34. Two of the tumors displayed partial losses restricted to one marker (D13S118 at 13q14 in tumor 1164, and D13S135 at 13q14.3-q22 in tumor 1398). We then determined the genomic structure of the ING1 gene and sequenced the entire coding region in 20 primary tumors showing 13q LOH and in five head and neck cancer cell lines. A single germline polymorphism was detected in 10 of the tumors analyzed (T to C change) located 110 nucleotides upstream of the starting methionine. No somatic mutations were found in any of the samples, suggesting that ING1 is not a tumor suppressor gene target in head and neck cancer. Genes Chromosomes Cancer 27:319-322, 2000.

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