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15.3 Percent With Melanoma Have Germline Likely/Pathogenic Variants

67 percent are in genes considered unrelated to melanoma

By Dermsquared Editorial Team | May 28, 2024

TUESDAY, May 28, 2024 -- Germline pathogenic/likely pathogenic (P/LP) variants occur in 15.3 percent of individuals with melanoma, according to a study published online March 19 in the Journal of the American Academy of Dermatology.

Pauline Funchain, M.D., from the Cleveland Clinic Foundation, and colleagues examined the incidence of hereditary melanoma and characterized the spectrum of cancer predisposition genes that may increase melanoma risk. Germline testing of more than 80 cancer predisposition genes was performed in 400 individuals with melanoma and a personal or family history of cancers.

The researchers found that 61 individuals (15.3 percent) with melanoma had germline P/LP variants. Most of these variants (67 percent) involved genes that were considered unrelated to melanoma, including BLM, BRIP1, CHEK2, MLH1, MSH2, PMS2, and RAD51C, while 33 percent were in genes previously associated with familial melanoma (BAP1, BRCA2, CDKN2A, MITF, and TP53). Overall, 46.9 percent of the P/LP variants were in homologous repair deficiency genes. In validation cohorts, P/LP rates were 10.6, 15.8, and 14.5 percent from an unselected oncologic cohort, a selected commercial testing cohort, and a highly selected dermatologic study, respectively.

"The prevalence of hereditary predisposition to cancer in individuals with melanoma is substantially higher than historical estimates and involves genes of clinical importance for the treatment and surveillance of both melanoma and noncutaneous cancers," the authors write.

Several authors disclosed ties to the pharmaceutical industry.


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