Sun-Related Risk Factors in Melanoma-Prone Families With CDKN2A Mutations

Extract

The CDKN2A gene encodes a lowmolecular- weight protein, p16, that inhibits the activity of the cyclin D1- cyclin-dependent kinase 4 complex (1). This enzyme complex phosphorylates the retinoblastoma protein, allowing the cell to progress through the G1 phase of the cell cycle. CDKN2A germline mutations have been detected in approximately 25% of melanoma-prone families. Deletions or mutations of the CDKN2A gene are common in melanomas grown in culture but less frequent in primary melanoma tumors (1–12). The identification of an unaffected individual homozygous for CDKN2A gene mutations (11) in addition to other mutation carriers without melanomas (12,13) suggests that other gene(s) and/ or environmental factors are involved in the pathogenesis of melanoma. To identify these other factors, we evaluated the risk of melanoma in relation to clinical, environmental, and genetic factors in American families with germline CDKN2A mutations that co-segregated with melanoma (13,14; Goldstein AM, Sikorski RS, Tucker MA: unpublished data).