Melanoma Genetics: From Susceptibility to Progression

Melanoma genetics has been for a long time a great challenge to cancer biologists, in part due to a complete lack of a single candidate gene to melanoma development. Differ‐ ent from breast and colorectal cancers, where BRCA-1/2 and APC/mismatch repair genes, respectively, characterize familial clusters of cancer susceptibility (reaching penetrance rates as high as 90% in some cases), in melanomas, the mutation rate of the most com‐ monly altered genes associated with disease progression do not exceed 60% of the cases in familial clusters. Among the “classical melanoma genes” are those coded at the CDKN2A locus (coding for p14 and p16, both related to cell cycle arrest), BRAF (specially the V600E mutation), a downstream transducer of the RAS signaling pathway and criti‐ cal for the cellular response to growth signals, and mutations in NRAS, somewhat relat‐ ed to initiation and progression of melanoma.