Gynecologic Melanoma: Genetics and Targetable Mutations

Melanomas of the female genital tract have unique molecular features that may be targetable using precision medicine, according to an article published in Cancer.¹

Only 1407 melanomas of the vulvar or vaginal regions were reported to the Surveillance, Epidemiology, and End Results (SEER) database between 1973 and 2010, though these diseases have a poor prognosis in contrast with cutaneous melanoma. For this literature-based paper, the authors compared molecular analyses of melanomas of the female genital tract with those of non-gynecologic melanomas to determine targeted treatment options for these rare cancers.

Of all cases reviewed from a sample of molecular profiles taken between 2009 and 2015, 51 melanomas of the genital tract and 2253 non-gynecologic melanomas were included. BRAF mutations were more common in genital tract cancers than non-gynecologic (26% vs 8.3%); KIT mutation was also most common among genital tract cancers.

PD-1 and PD-L1 expression was common in female genital tract melanomas; PI3KCA mutations were rare.

BRAF-mutant female genital tract cancers were likely to express TUBB3, which is associated with taxane resistance. In genital tract melanomas without KIT mutations, ERCC1 expression tended to be higher and O-6-methylguanine-DNA methyltransferase (MGMT) expression tended to be lower, suggesting resistance to platinum agents and sensitivity to alkylating agents.

The authors concluded that female genital tract melanomas are a unique molecular subtype of melanoma for which several mutations may be targetable using anti-cancer treatments.

Reference

1. Hou JY, Baptiste C, Hombalegowda RB, et al. Vulvar and vaginal melanoma: a unique subclass of mucosal melanoma based on a comprehensive molecular analysis of 51 cases compared with 2253 cases of nongynecologic melanoma. Cancer. 2016 Dec 27. doi: 10.1002/cncr.30473 [Epub ahead of print]