Abstract 5056: A glimpse into the somatic mutation landscape of melanoma through exome sequencing of 121 tumor-normal pairs

Melanoma is an aggressive skin cancer of melanocytic origin characterized by high metastatic potential and mutation rate. Affording a survey of the wide breadth of genomic lesions found in melanoma, we present here an analysis of the somatic mutations discovered in the sequenced exomes of 121 melanoma tumor-normal pairs. We identify frequent genomic alterations both in genes previously implicated in melanoma (BRAF, NRAS, TP53, CDKN2A, PTEN) as well as in several genes whose role in melanoma tumorigenesis has not yet been established and thus are of particular interest. To do so we implement a novel method to increase the identification of genes that are significantly recurrently mutated in melanoma in the setting of its exceptionally high mutation rate. A preponderance of C>T transitions (∼85%) in the observed mutational profile reflects a history of DNA damage due to UV radiation, though the majority of somatic mutations in known melanoma genes are not C>T events. Our study broadens understanding of the genomic lesions involved in melanoma tumorigenesis, and we expect our analysis approach to inform future genomic studies of cancer lineages with similarly high mutation rates. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5056. doi:1538-7445.AM2012-5056