Germline CDKN2A Variant Cascade Testing Across Four Generations Reveals Familial Melanoma-Breast Cancer...

Area of Science:

• Genetics
• Oncology
• Hereditary Cancer Syndromes

Background:

• The CDKN2A gene is a known tumor suppressor gene.
• Mutations in CDKN2A are associated with hereditary melanoma.
• The role of CDKN2A in hereditary breast cancer is less understood.

Purpose of the Study:

• To investigate the co-segregation of a pathogenic CDKN2A variant within a four-generation family.
• To determine the association between the CDKN2A variant and the development of melanoma and breast cancer.

Main Methods:

• Pedigree analysis was conducted across four generations.
• Genetic testing was performed to identify carriers of the CDKN2A variant.
• Clinical data, including cancer diagnoses and age of onset, were collected for family members.

Main Results:

• A pathogenic CDKN2A variant was identified in 18 individuals across four generations.
• Eleven carriers developed multiple melanomas, with diagnoses from adolescence to fifties.
• Six female carriers were diagnosed with breast cancer, with onset from their thirties to sixties.
• Additional cancers, including pancreatic and head and neck cancers, were observed in carriers.

Conclusions:

• The study demonstrates the co-segregation of a pathogenic CDKN2A variant with both melanoma and breast cancer.
• This suggests a potential genotype-phenotype correlation linking the CDKN2A variant to a hereditary cancer syndrome encompassing multiple cancer types.
• Further research is warranted to elucidate the full spectrum of cancers associated with this CDKN2A variant.