WP4685 - Melanoma - Homo sapiens

Melanoma, or malignant melanoma, is a highly aggressive cancer that develops in melanocytes. Many genes have been found to be mutated or amplified in melanoma, with the most commonly mutated genes being BRAF, CDKN2A, NRAS and TP53. MAPK and PI3K/Akt signaling are central to melanoma.

This pathway is a summary of information from figures 1 and 2 from [Kunz and Vera](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520749/) and supplemented with information from [KEGG](https://www.kegg.jp/dbget-bin/www_bget?pathway+hsa05218).

CDKN2A is frequently mutated in melanoma and germline mutations are associated with an increased susceptibility of developing skin cancer. The CDKN2A encodes two proteins, p16 (INK4A) and p14ARF, with different functions. p16 binds to CDK4, which prevents phosphorylation of Rb, thereby controlling the G1 to S transition. Without functioning p16, G1 to S transition can proceed. p14ARF is central to cell cycle regulation, inhibiting MDM2, which normally degrades p53, so loss of p14ARF has a similar effect to loss of p53.