Shared Mutations in Skin & Conjunctival Melanomas

Article: Ultraviolet radiation causes rare type of eye cancer
Source: University of Manchester (U.K.)
Published: January 11, 2021

Mutation spectra in mucosal and common cutaneous melanomas

Researchers in the U.K. studying how ultraviolet radiation contributes to cutaneous melanomas found that the same genes that cause these skin cancers also cause a rarer form of melanoma of the eye, namely, conjunctival melanoma, of the mucous membrane that lines the sclera of the eye and inner lids. In particular, the researchers applied whole genome sequencing to 10 samples of conjunctival melanomas and found UVR-associated single base substitution signature 7 (SBS7) genetic mutations in 9 of the conjunctival melanomas, as compared to 1 sample of conjunctival melanoma and 8 samples of other mucosal melanomas that did not show these features related to ultraviolet radiation. They argue that SBS7 dominance in mucosal melanoma is a better indicator of UVR-exposure than tumor site. Furthermore, they found that ultraviolet radiation-induced conjunctival melanomas contain the same cancer mutations in the BRAF and NRAS genes. This contrasts with earlier understanding that the KIT and SF3B1 mutations are more common in mucosal melanomas and the BRAF and NRAS mutations are more common in cutaneous melanomas. Although uveal melanomas, another rare melanoma of the eye, are less related to ultraviolet radiation, the researchers report that their findings complement an earlier study showing that ultraviolet exposure can present SBS7 predominance if it arises on the iris. A common driver of both cutaneous and conjunctival melanoma, the researchers argue, facilitates the application of therapies developed primarily for cutaneous melanoma in the context of ocular melanomas, such as the BRAF inhibitor vemurafenib used to treat skin melanoma. The lead author of the study comments, “Our work shows the importance of delving into the underlying biology in rare cancers, which could identify new tailored treatment avenues for people. In this case we have identified mutations in a rare type of eye cancer that could be targeted by drugs used to treat skin cancer.”

My rating of this study: ⭐⭐

Mundra P, Dhomen N, Rodrigues M, et al. "Ultraviolet radiation drives mutations in a subset of mucosal melanomas." Nature Communications.  12:259. 11 January 2021. https://doi.org/10.1038/s41467-020-20432-5