Normal repair of ultraviolet radiation-induced DNA damage in familial melanoma without CDKN2A or CDK4 gene mutation

Excessive sun exposure and family history are strong risk factors for the d evelopment of cutaneous melanoma. Inherited susceptibility to this type of skin cancer could therefore result from constitutively impaired capacity to repair ultraviolet (UV)-induced DNA lesions. While a proportion of familia l melanoma kindreds exhibit germline mutations in the cell cycle regulatory gene CDKN2A (p16(INK4a)) or its protein target, cyclin-dependent kinase 4 (CDK4), the biochemical basis of most familial melanoma is unknown, We have examined lymphoblastoid cell lines from melanoma-affected and unaffected i ndividuals from large hereditary melanoma kindreds which are not attributab le to CDKN2A or CDK4 gene mutation. These lines were tested for sensitivity of clonogenic growth to UV radiation and for their ability to repair trans fected UV-damaged plasmid templates (host cell reactivation). Two of seven affected-unaffected pairs differed In colony survival after exposure to UVB radiation; however, no significant differences were observed in the host-c ell reactivation assays. These results indicate that melanoma susceptibilit y genes other than CDKN2A and CDK4 do not impair net capacity to repair UV- induced DNA damage. (C) 1999 Lippincott Williams & Wilkins.