Germline CDKN2A Variant Cascade Testing Across Four Generations Reveals Familial Melanoma–Breast Cancer Genotype–Phenotype Correlation

This study reports co-segregation of a pathogenic CDKN2A variant with both melanoma and breast cancer in a four-generation pedigree. Eighteen individuals were test positive (n = 10), obligate (n = 5) or assumed carriers (n = 3) of the CDKN2A variant. Eleven of these had multiple melanomas, with initial diagnoses from teens to fifties. Six of thirteen female carriers had breast cancer (n = 5 test positive, n = 1 assumed carrier), with diagnoses ranging from thirties to sixties. Additional cancer diagnoses included pancreatic, and head and neck cancers. This study illustrates a possible genotype–phenotype association between a pathogenic CDKN2A variant and the co-occurrence of melanoma and breast cancer in a hereditary context.