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 development 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 familial melanoma kindreds exhibit germline mutations in the cell cycle regulatory gene CDKN2A (p16INK4a) 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 individuals from large hereditary melanoma kindreds which are not attributable to CDKN2A or CDK4 gene mutation. These lines were tested for sensitivity of clonogenic growth to UV radiation and for their ability to repair transfected 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-cell reactivation assays. These results indicate that melanoma susceptibility genes other than CDKN2A and CDK4 do not impair net capacity to repair UV-induced DNA damage.
Shannon
J A
JA
Westmead Institute for Cancer Research, University of Sydney, NSW, Australia. jennys@hemonc.wh.su.edu.au
Matias
C
C
Luxford
C
C
Kefford
R F
RF
Mann
G J
GJ
D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects*; D019942:Genes, p16 / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011518:Proto-Oncogene Proteins; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays / Q000009:adverse effects*
D011518:Proto-Oncogene Proteins; D015500:Chloramphenicol O-Acetyltransferase; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases