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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Mutation of the CDKN2A 5' UTR creates an aberrant initiation codon and predisposes to melanoma.

Approximately 8-12% of melanoma is inherited in an autosomal dominant fashion with variable penetrance. A chromosome 9p21 locus has been linked to this disease in 50-80% of affected families. CDKN2A (also known as P16, INK4, p16INK4A and MTS1) is allelic to this locus and encodes a cdk4/cdk6 kinase inhibitor that constrains cells from progressing through the G1 restriction point. Although germline CDKN2A coding mutations cosegregate with melanoma in 25-60% of families predisposed to the disease, there remains a number of mutation-negative families that demonstrate linkage of inherited melanoma to 9p21 markers. We show here that a subset of these kindreds possess a G-->T transversion at base -34 of CDKN2A, designated G-34T. This mutation gives rise to a novel AUG translation initiation codon that decreases translation from the wild-type AUG. The G-34T mutation is not seen in controls, segregates with melanoma in families and, on the basis of haplotyping studies, probably arose from a common founder in the United Kingdom. Characterization of this and other CDKN2A non-coding mutations should have an impact on current efforts to identify susceptible melanoma-prone families and individuals.[1]


  1. Mutation of the CDKN2A 5' UTR creates an aberrant initiation codon and predisposes to melanoma. Liu, L., Dilworth, D., Gao, L., Monzon, J., Summers, A., Lassam, N., Hogg, D. Nat. Genet. (1999) [Pubmed]
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