Lack of germline CDK6 mutations in familial melanoma

Germline mutations in genes encoding several components of the retinoblasto ma pathway have been linked with inherited predisposition to melanoma, Most commonly, such mutations involve CDKN2A, a cyclin-dependant kinase inhibit or of two kinases, CDK4 and CDK6, which phosphorylate the retinoblastoma pr otein (pRB) and thereby promote passage through the G(1)/S cell-cycle restr iction point. Less frequently, germline mutations in the CDK4 gene have als o been linked with an increased risk of melanoma, Despite the sequence and functional homology between CDK4 and CDK6, the role of germline mutations i n CDK6 in melanoma predisposition is unknown. We detected no CDK6 mutations within the p16 (CDKN2A) binding domain in index cases from 60 melanoma-pro ne kindreds that lacked germline mutations in the coding regions of either CDKN2A or within the entire CDK4 coding region. We conclude that germline m utations in CDK6 do not make a significant contribution to melanoma predisp osition.