CDKN2A (P16INK4a) and CDK4 mutation analysis in 131 Australian melanoma probands: Effect of family history and multiple primary melanomas

✍ Scribed by Elizabeth A. Holland; Helen Schmid; Richard F. Kefford; Graham J. Mann

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 180 KB
• Volume: 25
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/(sici)1098-2264(199908)25:4<339::aid-gcc5>3.0.co;2-h

✦ Synopsis

Mutation analysis of two genes involved in melanoma susceptibility (CDKN2A/p16 INK4a and CDK4) was undertaken in 131 probands with a family history of melanoma. Screening of all three exons of CDKN2A and exon 2 of CDK4 by single-strand conformation polymorphism (SSCP) analysis and/or direct sequencing identified a total of 10 different CDKN2A germline mutations, including 6 not previously described in the germline. All but one has been previously proven to, or is likely to, affect the structure and function of p16 INK4a . The incidence of CDKN2A mutation was 8.4% (11/131), but was significantly higher in families with three or more cases of melanoma (10/66, 15.1%) than in those in which only two relatives were affected (1/65, 1.5%). The incidence of CDKN2A mutation was also higher in families with three or more cases of melanoma and at least one member with multiple primary melanomas (6/19, 31.6%) than in similar families without multiple primary melanomas (4/47, 8.5%). One novel CDK4 variant of uncertain significance was found in a kindred that also carries a CDKN2A mutation.