Abstract

Advances in high-throughput genomic technologies provide an unprecedented opportunity to systematically interrogate the genetic landscape of melanoma. As genomic sequences are increasingly becoming available they provide biologically and clinically relevant information on the complexity of the melanoma genome. We have recently compiled sequence data from >500 melanoma genomes/exomes, the largest melanoma dataset to date. We have validated recurrent alterations in ~500 cutaneous melanomas and have identified almost 50 alterations that occur in five or more melanoma cases. We thus have identified a large number of candidate driver genes which may hold promise for the design of novel therapies to treat melanoma. Importantly, synonymous mutations, which do not alter the protein sequence, are rarely investigated in the cancer genomics field. Our analysis identified for the first time a recurrent functional synonymous somatic mutation in BCL2L12 (F17F). Our data indicate that “silent” alterations have a role to play in human cancer, emphasizing the importance of their investigation in future cancer genome studies.