Research IndicatorsGraph generated 31 August 2019 using data from PubMed using criteria.
Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic. Tag cloud generated 30 August, 2019 using data from PubMed, MeSH and CancerIndex
Specific Cancers (3)
Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.
Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).
OMIM, Johns Hopkin University
Referenced article focusing on the relationship between phenotype and genotype.
International Cancer Genome Consortium.
Summary of gene and mutations by cancer type from ICGC
Cancer Genome Anatomy Project, NCI
COSMIC, Sanger Institute
Somatic mutation information and related details
GEO Profiles, NCBI
Search the gene expression profiles from curated DataSets in the Gene Expression Omnibus (GEO) repository.
Latest Publications: CACNA1G (cancer-related)
Miller CT, Chen G, Gharib TG, et al.Increased C-CRK proto-oncogene expression is associated with an aggressive phenotype in lung adenocarcinomas.
Oncogene. 2003; 22(39):7950-7 [PubMed
] Related Publications
The C-CRK gene, cellular homolog of the avian v-crk oncogene, encodes two alternatively spliced adaptor signaling proteins, CRKI (28 kDa) and CRKII (40 kDa). Both CRKI and CRKII have been shown to activate kinase signaling and anchorage-independent growth in vitro and CRKI transformed cells readily form tumors in nude mice. Affymetrix oligonucleotide arrays were used to analyse 86 lung adenocarcinomas and 10 uninvolved lung tissues. C-CRK mRNA expression was increased in more advanced (stage III versus stage I), larger (T(2-4) versus T(1)), and poorly differentiated tumors and in tumors from patients demonstrating poor survival (P=0.00034). An overlapping series of 93 lung adenocarcinomas (64 stage I and 29 stage III) and 10 uninvolved lung specimens were measured for quantitative differences in CRKI and CRKII protein levels using 2-D PAGE. CRK protein spots were identified using mass spectrometry and 2-D Western blotting. A significant increase in levels of the CRKI oncoprotein and the phosphorylated isoform of CRKII was observed in tumors (P<0.05). No difference in protein level was evident between stages. Concordant with mRNA expression, CRKI and CRKII were increased in poorly differentiated tumors (P<0.05). CRK immunohistochemical analysis of tumor tissue arrays using the same tumor series also demonstrated increased abundance of nuclear and cytoplasmic CRK in more proliferative tumors (P<0.05). This study provides the first quantitative analysis of discrete CRKI and CRKII protein isoforms in human lung tumors and provides evidence that the C-CRK proto-oncogene may foment a more aggressive phenotype in lung cancers.
Sorensen PH, Lynch JC, Qualman SJ, et al.PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the children's oncology group.
J Clin Oncol. 2002; 20(11):2672-9 [PubMed
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PURPOSE: Alveolar rhabdomyosarcoma (ARMS) is an aggressive soft tissue malignancy of children and adolescents. Most ARMS patients express PAX3-FKHR or PAX7-FKHR gene fusions resulting from t(2;13) or t(1;13) translocations, respectively. We wished to confirm the diagnostic specificity of gene fusion detection in a large cohort of RMS patients and to evaluate whether these alterations influence clinical outcome in ARMS.
PATIENTS AND METHODS: We determined PAX3-FKHR or PAX7-FKHR fusion status in 171 childhood rhabdomyosarcoma (RMS) patients entered onto the Intergroup Rhabdomyosarcoma Study IV, including 78 ARMS patients, using established reverse transcriptase polymerase chain reaction assays. All patients received central pathologic review and were treated using uniform protocols, allowing for meaningful outcome analysis. We examined the relationship between gene fusion status and clinical outcome in the ARMS cohort.
RESULTS: PAX3-FKHR and PAX7-FKHR fusion transcripts were detected in 55% and 22% of ARMS patients, respectively; 23% were fusion-negative. All other RMS patients lacked transcripts, confirming the specificity of these alterations for ARMS. Fusion status was not associated with outcome differences in patients with locoregional ARMS. However, in patients presenting with metastatic disease, there was a striking difference in outcome between PAX7-FKHR and PAX3-FKHR patient groups (estimated 4-year overall survival rate of 75% for PAX7-FKHR v 8% for PAX3-FKHR; P =.0015). Multivariate analysis demonstrated a significantly increased risk of failure (P =.025) and death (P =.019) in patients with metastatic disease if their tumors expressed PAX3-FKHR. Among metastatic ARMS, bone marrow involvement was significantly higher in PAX3-FKHR-positive patients.
CONCLUSION: Not only are PAX-FKHR fusion transcripts specific for ARMS, but expression of PAX3-FKHR and PAX7-FKHR identifies a very high-risk subgroup and a favorable outcome subgroup, respectively, among patients presenting with metastatic ARMS.
Qualman SJ, Coffin CM, Newton WA, et al.Intergroup Rhabdomyosarcoma Study: update for pathologists.
Pediatr Dev Pathol. 1998 Nov-Dec; 1(6):550-61 [PubMed
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Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood, and 75% of such cases in the United States are reviewed at the Pathology Center for the Intergroup Rhabdomyosarcoma Study Group (IRSG). The first four generations of IRSG therapeutic trials (IRS I-IV) and supportive pathologic studies have generated a new International Classification of Rhabdomyosarcoma (ICR) that offers new morphologic concepts to the practicing pathologist. The objective of this report is to clearly define emerging histopathologic categories of RMS as defined by the ICR, and to emphasize correlative immunohistochemical or molecular studies. Emerging ICR variants of RMS place the patient in widely divergent prognostic categories (superior, botryoid or spindle cell variants; poor, solid alveolar or diffusely anaplastic variants). The cardinal histopathologic features of the ICR combined with results of studies of fusion genes seen with t(1;13) and t(2;13) will help delineate therapeutic subgroups of RMS for the fifth generation (IRS V) of IRSG studies. Consequently, it is imperative for the practicing pathologist to be familiar with the practical workup and diagnosis of RMS in childhood.
Weiner LM, Clark JI, Davey M, et al.Phase I trial of 2B1, a bispecific monoclonal antibody targeting c-erbB-2 and Fc gamma RIII.
Cancer Res. 1995; 55(20):4586-93 [PubMed
] Related Publications
2B1 is a bispecific murine monoclonal antibody (BsMAb) with specificity for the c-erbB-2 and Fc gamma RIII extracellular domains. This BsMAb promotes the targeted lysis of malignant cells overexpressing the c-erbB-2 gene product of the HER2/neu proto-oncogene by human natural killer cells and mononuclear phagocytes expressing the Fc gamma RIII A isoform. In a Phase I clinical trial of 2B1, 15 patients with c-erbB-2-overexpressing tumors were treated with 1 h i.v. infusions of 2B1 on days 1, 4, 5, 6, 7, and 8 of a single course of treatment. Three patients were treated with daily doses of 1.0 mg/m2, while six patients each were treated with 2.5 mg/m2 and 5.0 mg/m2, respectively. The principal non-dose-limiting transient toxicities were fevers, rigors, nausea, vomiting, and leukopenia. Thrombocytopenia was dose limiting at the 5.0 mg/m2 dose level in two patients who had received extensive prior myelosuppressive chemotherapy. Murine antibody was detectable in serum following 2B1 administration, and its bispecific binding properties were retained. The pharmacokinetics of this murine antibody were variable and best described by nonlinear kinetics with an average t 1/2 of 20 h. Murine antibody bound extensively to all neutrophils and to a proportion of monocytes and lymphocytes. The initial 2B1 treatment induced more than 100-fold increases in circulating levels of tumor necrosis factor-alpha, interleukin 6, and interleukin 8 and lesser rises in granulocyte-monocyte colony-stimulating factor and IFN-gamma. Brisk human anti-mouse antibody responses were induced in 14 of 15 patients. Several minor clinical responses were observed, with reductions in the thickness of chest wall disease in one patient with disseminated breast cancer. Resolution of pleural effusions and ascites, respectively, were noted in two patients with metastatic colon cancer, and one of two liver metastases resolved in a patient with metastatic colon cancer. Treatment with 2B1 BsMAb has potent immunological consequences. The maximum tolerated dose and Phase II daily dose for patients with extensive prior myelosuppressive chemotherapy was 2.5 mg/m2. Continued dose escalation is required to identify the maximally tolerated dose for patients who have been less heavily pretreated.
Burnett RC, Thirman MJ, Rowley JD, Diaz MOMolecular analysis of the T-cell acute lymphoblastic leukemia-associated t(1;7)(p34;q34) that fuses LCK and TCRB.
Blood. 1994; 84(4):1232-6 [PubMed
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Previously we had characterized the t(1;7)(p34;q34) translocation from HSB-2. This translocation fused the beta T-cell receptor gene (TCRB) constant region and transcriptional enhancer with the type I transcription unit of the LCK gene on the derivative 1 [der(1)] chromosome. The type II promoter was translocated to the der(7) chromosome. Regarding the mechanism of the t(1;7) in HSB-2, we identified an alternating purine-pyrimidine tract (G-T)17 at the 1p34/LCK breakpoint. Additionally, sequence analysis of both breakpoint junctions provided data that implicate the V(D)J recombinase in formation of the t(1;7). A heptamer-nonamer recognition sequence with a 12-bp spacer was found in the immediate vicinity of the 1p34/LCK breakpoint and, thus, chromosomal breakage at 1p34 may be explained as resulting from recombinase activity. Because phosphorylation of Tyr-505 in vivo regulates the tyrosine kinase activity of p56lck we amplified a region from LCK exon 12 that contains the codon for Tyr-505 and showed no mutation of this codon in HSB-2 DNA and, therefore, p56lck in HSB-2 is not activated by mutation of Tyr-505. We have analyzed LCK gene expression in HSB-2 and SUP-T12 cell lines. RNase protection analysis identified almost exclusively type I transcripts in HSB-2. An independent t(1;7) in SUP-T12 also resulted in the juxtaposition of LCK to TCRB. The breakpoint in SUP-T12 occurred 2 kb 5' of the type II promoter, leaving an intact LCK gene on the der(1) chromosome. RNase protection analysis identified both type I and type II LCK transcripts in a 3:1 ratio in SUP-T12. Factors other than proximity to the TCRB enhancer must affect promoter utilization in this cell line.
SCL gene disruptions are the most common chromosomal abnormality associated with the development of T cell acute lymphoblastic leukemia (ALL). Such disruptions can be the result of t(1;14) and t(1;7) translocations, as well as a cytogenetically undetectable interstitial deletion of chromosome 1. We present here a case of T cell ALL with a t(1;3)(p34;p21) translocation that also disrupts the SCL locus and leads to dysregulated SCL gene expression. This translocation, similar to previously reported SCL gene disruptions, appears to have been mediated, at least in part, by the V(D)J recombinase complex, since cryptic heptamer recognition sequences, as well as nontemplated N region nucleotide addition, are present at the breakpoints. The t(1;3) also disrupts a region on chromosome 3 characterized by alternating purine and pyrimidine residues, which can form a Z-DNA structure, reported to be prone to recombination events. A previously undescribed, evolutionarily conserved transcript unit is detected within 8 kb of the breakpoint on chromosome 3. This report extends the spectrum of recognized SCL translocations associated with T cell ALL, and underscores the contention that dysregulated SCL expression may be a causal event in T cell ALL.
Fitzgerald TJ, Neale GA, Raimondi SC, Goorha RMc-tal, a helix-loop-helix protein, is juxtaposed to the T-cell receptor-beta chain gene by a reciprocal chromosomal translocation: t(1;7)(p32;q35).
Blood. 1991; 78(10):2686-95 [PubMed
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Studies on nonrandom chromosomal translocations have been important for the identification of genes potentially involved in the malignant transformation of cells. The most widely studied translocations, involving members of the Ig supergene family, have shown juxtapositions of proto-oncogenes with the rearranging loci. Such translocations can inappropriately activate expression of the proto-oncogenes and thereby play a role in tumorigenesis. Because the cytogenetic analysis of a bone marrow sample from a child with T-cell acute lymphoblastic leukemia showed a (1;7)(p32;q35) translocation, we sought to determine if the translocation breakpoint was in the T-cell receptor (TCR)-beta gene locus on chromosome 7. Analysis of the TCR-beta gene by Southern blotting showed three rearranged bands. Nucleotide sequencing and Southern blot analysis of TCR-beta genomic clones, isolated from patient DNA, showed that one contained a normal rearrangement of the TCR-beta gene using V beta 12.2, D beta 2.1, and J beta 2.5, whereas two other clones contained DNA from derivative chromosomes 1 and 7. Chromosomal mapping showed that the (1;7) translocation breakpoint was 35 kb 3' to the c-tal gene locus. The juxtaposition of c-tal to the TCR-beta locus may enhance c-tal expression and contribute to T-cell leukemogenesis.
A case of T lymphoblastic leukemia (T-ALL) showing t(1;7)(p34;q34) as the sole karyotypic abnormality was investigated at the molecular level. Screening of a phage library of tumor DNA with a probe for the beta T cell receptor gene (TCRB), which maps to chromosomal band 7q34, resulted in the isolation of a clone containing DNA spanning the translocation breakpoint of the der(1) chromosome. This clone contained chromosome 1 DNA juxtaposed upstream of a D beta-J beta joint. Cloning of the corresponding germline region of chromosome 1 resulted in the isolation of a phage containing the breakpoint from the reciprocal, der(7), product, which showed chromosome 1 DNA joined downstream to a V beta segment. Comparison of germline and translocation clones demonstrated that breakage of chromosome 1 had occurred at the border of a tandem repeat of Alu sequences. To search for transcripts from DNA near the breakpoint, a chromosomal walk was initiated along chromosome 1. A probe consisting of chromosome 1 DNA from 24-30 kb upstream of the breakpoint hybridized to a transcript derived from the gene encoding the lymphocyte-specific tyrosine kinase p56lck, previously mapped to chromosomal band 1p34. The nonrandom nature of the breakpoints in this case was confirmed by the analysis of a second independent case of T-ALL containing a t(1;7) translocation, which was also found to show breakage within the LCK locus. The chromosomal breakpoint in the first case was localized 2 kb upstream of the lck upstream promoter and first nontranslated exon, while the breakpoint of the second case lay between the two alternative lck promoters, upstream of the second exon. Relative to normal thymus and activated T cells, levels of lck mRNA were greatly elevated in the first case and moderately elevated in the second. The existence of these translocations raises the possibility that alterations in the promoter region of the LCK locus may play a role in human cancer.
Chaganti RS, Balazs I, Jhanwar SC, et al.The cellular homologue of the transforming gene of SKV avian retrovirus maps to human chromosome region 1q22----q24.
Cytogenet Cell Genet. 1986; 43(3-4):181-6 [PubMed
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We report the chromosomal localization of the cellular oncogene SKI, the putative oncogene of the Sloan-Kettering viruses (SKVs), a group of transforming retroviruses that had been isolated from chicken embryo cells infected with the avian leukosis virus tdB77. Southern blot analysis of DNA from mouse X human somatic cell hybrids with the v-SKI probe established synteny with chromosome 1, but excluding the region 1pter----q21. In situ hybridization of the same probe both to human spermatocyte pachytene and lymphocyte metaphase chromosomes enabled precise localization of the gene to the region 1q22----q24, a region that frequently is involved in translocations and other rearrangements in diverse human tumor types. In situ hybridization studies of metaphase spreads from a small noncleaved cell lymphoma that exhibited a t(1;14)(q21;q32) translocation showed that SKI translocates to the der(14) chromosome. Cytogenetic analysis of 65 prospectively ascertained non-Hodgkin's lymphomas revealed that the SKI region undergoes nonrandom breakage leading to translocations. Further analysis of the chromosome breaks in this group of lymphomas suggested that those involving the SKI site probably are of importance in tumor progression.