Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The methylthioadenosine phosphorylase (mtap) gene is localized on chromosome 9p21, a chromosomal region often affected by deletion in several kinds of malignant tumors. Studies on malignant melanoma have revealed loss of MTAP expression in vitro and in vivo; however, loss of MTAP expression is mainly regulated by promoter hypermethylation. Loss of MTAP was shown to have an effect on tumor invasion and metastasis. In a recent study, MTAP not only had a role as tumor suppressor but was also implicated in lack of therapeutic response of patients with recurrent malignant melanoma. There is evidence that loss of MTAP results in an inhibition of STAT signaling pathways regulated by interferon. This in turn leads to ineffectiveness of interferon therapy. Determination of the MTAP status in the primary tumor could, therefore, potentially lead to a selection of patients who benefit from interferon treatment.
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PMID:A potential predictive marker for response to interferon in malignant melanoma. 1753 37

The utility of tumor-derived cell lines is dependent on their ability to recapitulate underlying genomic aberrations and primary tumor biology. Here, we sequenced the exomes of 25 bladder cancer (BCa) cell lines and compared mutations, copy number alterations (CNAs), gene expression and drug response to BCa patient profiles in The Cancer Genome Atlas (TCGA). We observed a mutation pattern associated with altered CpGs and APOBEC-family cytosine deaminases similar to mutation signatures derived from somatic alterations in muscle-invasive (MI) primary tumors, highlighting a major mechanism(s) contributing to cancer-associated alterations in the BCa cell line exomes. Non-silent sequence alterations were confirmed in 76 cancer-associated genes, including mutations that likely activate oncogenes TERT and PIK3CA, and alter chromatin-associated proteins (MLL3, ARID1A, CHD6 and KDM6A) and established BCa genes (TP53, RB1, CDKN2A and TSC1). We identified alterations in signaling pathways and proteins with related functions, including the PI3K/mTOR pathway, altered in 60% of lines; BRCA DNA repair, 44%; and SYNE1-SYNE2, 60%. Homozygous deletions of chromosome 9p21 are known to target the cell cycle regulators CDKN2A and CDKN2B. This loci was commonly lost in BCa cell lines and we show the deletions extended to the polyamine enzyme methylthioadenosine (MTA) phosphorylase (MTAP) in 36% of lines, transcription factor DMRTA1 (27%) and antiviral interferon epsilon (IFNE, 19%). Overall, the BCa cell line genomic aberrations were concordant with those found in BCa patient tumors. We used gene expression and copy number data to infer pathway activities for cell lines, then used the inferred pathway activities to build a predictive model of cisplatin response. When applied to platinum-treated patients gathered from TCGA, the model predicted treatment-specific response. Together, these data and analysis represent a valuable community resource to model basic tumor biology and to study the pharmacogenomics of BCa.
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PMID:Molecular analysis of urothelial cancer cell lines for modeling tumor biology and drug response. 2727 Apr 41