February 2018 - Vol 138 No 2

Schematic showing the RAS/RAF/MEK pathway as well as the PI3K/AKT pathway. Genes or proteins are shown with their relative mutation distributions among dorsal, volar, and subungual melanomas with dorsal in red, volar in blue, and subungual in green. The sun symbol indicates UV predominant pathways. Activation of the PI3K/AKT pathway, primarily through silencing of PTEN, is a frequent finding in BRAF-mutated melanomas. Mutations in the catalytic subunit of PI3K (PIK3CA) were found with high frequency in our sun-shielded melanomas. This mutation is relatively uncommon in sun-exposed melanoma, and may represent an alternative means of PI3K/AKT pathway activation in sun-shielded tumors. AKT, acutely transforming retrovirus AKT8 in rodent T-cell lymphoma; ERK, extracellular signal–regulated kinase; MEK, mitogen activated protein kinase; mTOR, mechanistic target of rapamycin; PI3K, phosphatidylinositol-3-kinase.

Haugh and coworkers characterized acral melanocytic melanomas on dorsal, volar, and subungal/interdigital skin using next generation sequencing of a 50 gene panel. They detected mutation heterogeneity that may reflect differential UV exposure. See page 384 for details.