Rarity of CDK4 germline mutations in familial melanoma
作者:
A. Goldstein,
A. Chidambaram,
A. Halpern,
E. Holly,
D. Guerry,
R. Sagebiel,
D. Elder,
M. Tucker,
期刊:
Melanoma Research
(OVID Available online 2002)
卷期:
Volume 12,
issue 1
页码: 51-55
ISSN:0960-8931
年代: 2002
出版商: OVID
关键词: Arg24Cys mutation;CMM;cyclin-dependent kinase 4;penetrance
数据来源: OVID
摘要:
To date, two genes have been implicated in melanoma pathogenesis. The first,CDKN2A, is a tumour suppressor gene with germline mutations detected in 20% of melanoma-prone families. The second,CDK4, is an oncogene with co-segregating germline mutations detected in only three kindreds worldwide. We examined 16 American melanoma-prone families for mutations in all coding exons ofCDK4and screened additional members of two previously reported families with the Arg24Cys germlineCDK4mutation to evaluate the penetrance of the mutation. No newCDK4mutations were identified. In the two Arg24Cys families, the penetrance was estimated to be 63%. Overall, 12 out of 12 invasive melanoma patients, none out of onein situmelanoma patient, five out of 13 dysplastic naevi patients, two out of 15 unaffected family members, and none out of 10 spouses carried the Arg24Cys mutation. Dysplastic naevi did not strongly co-segregate with the Arg24Cys mutation. Thus the phenotype observed in melanoma-proneCDK4families appears to be more complex than just theCDK4mutation. Both genetic and environmental factors are likely to contribute to the occurrence of melanoma and dysplastic naevi in these families. In summary, althoughCDK4is a melanoma susceptibility gene, it plays a minor role in hereditary melanoma.
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