Gynecologic Melanoma: Genetics and Targetable Mutations

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Melanomas of the female genital tract have unique molecular features that may be targetable using precision medicine.
Melanomas of the female genital tract have unique molecular features that may be targetable using precision medicine.

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.

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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]
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