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Novel somatic and germline mutations in cancer candidate genes in glioblastoma, melanoma, and pancreatic carcinoma.

Authors
  • Balakrishnan, Asha
  • Bleeker, Fonnet E
  • Lamba, Simona
  • Rodolfo, Monica
  • Daniotti, Maria
  • Scarpa, Aldo
  • van Tilborg, Angela A
  • Leenstra, Sieger
  • Zanon, Carlo
  • Bardelli, Alberto
Type
Published Article
Journal
Cancer research
Publication Date
Apr 15, 2007
Volume
67
Issue
8
Pages
3545–3550
Identifiers
PMID: 17440062
Source
Medline
License
Unknown

Abstract

A recent systematic sequence analysis of well-annotated human protein coding genes or consensus coding sequences led to the identification of 189 genes displaying somatic mutations in breast and colorectal cancers. Based on their mutation prevalence, a subset of these genes was identified as cancer candidate (CAN) genes as they could be potentially involved in cancer. We evaluated the mutational profiles of 19 CAN genes in the highly aggressive tumors: glioblastoma, melanoma, and pancreatic carcinoma. Among other changes, we found novel somatic mutations in EPHA3, MLL3, TECTA, FBXW7, and OBSCN, affecting amino acids not previously found to be mutated in human cancers. Interestingly, we also found a germline nucleotide variant of OBSCN that was previously reported as a somatic mutation. Our results identify specific genetic lesions in glioblastoma, melanoma, and pancreatic cancers and indicate that CAN genes and their mutational profiles are tumor specific. Some of the mutated genes, such as the tyrosine kinase EPHA3, are clearly amenable to pharmacologic intervention and could represent novel therapeutic targets for these incurable cancers. We also speculate that similar to other oncogenes and tumor suppressor genes, mutations affecting OBSCN could be involved in cancer predisposition.

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