J Med Genet 1999;36:490-493 ( June )

Short report

CDKN2A mutations in Spanish cutaneous malignant melanoma families and patients with multiple melanomas and other neoplasia Anna Ruiz^a, Susana Puig^b, Josep Malvehy^b, Conxi Lázaro^a, Michael Lynch^a, Anna M Gimenez-Arnau^c, Lluis Puig^d, Julian Sánchez-Conejo^e, Xavier Estivill^a, Teresa Castel^b

^a Medical and Molecular Genetics Centre-IRO, Hospital Duran i Reynals, Avia Castelldefels, Km 2.7, L'Hospitalet de Llobregat, 08907 Barcelona, Catalonia, Spain, ^b Dermatology Service, Hospital Clínic, Barcelona, Catalonia, Spain, ^c Dermatology Service, Hospital del Mar, Barcelona, Catalonia, Spain, ^d Dermatology Service, Hospital de Sant Pau, Barcelona, Catalonia, Spain, ^e Dermatology Service, Hospital Virgen del Rocio, Sevilla, Spain

Correspondence to: Dr Estivill.

Received 5 August 1998; Revised version accepted for publication 28 January 1999

The CDKN2A gene has been implicated in cutaneous malignant melanoma (CMM) in about 40% of families with linkage to chromosome 9p21, while a small proportion of families have mutations in the CDK4 gene. In order to estimate the importance of these genes in the predisposition to CMM in Spanish families and patients we have analysed, by SSCA, a total of 56 subjects belonging to 34 CMM families, and nine patients with multiple CMM and other neoplasia. We have detected germline CDKN2A mutations in six out of the 34 families (17%). A frameshift mutation (358delG) and four missense mutations (G59V, G101W (two cases), D84Y, and R87W) were identified. Five CMM patients from different families (14%) carried the A148T variant, which is known not to affect p16 activity. No mutations were detected in the patients with multiple CMM or other neoplasms. We have not found mutations either in exon 1 of the CDKN2A gene or in exon 2A of CDK4. Linkage analysis of the 9p21 region showed exclusion for one of the families for CMM and for four families for CMM/dysplastic naevi. This study indicates a small role for CDKN2A in Spanish CMM families and suggests that other genes are also responsible for CMM predisposition.


Keywords: cutaneous malignant melanoma; CDKN2A; p16; CDK4

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© 1999 by J Med Genet
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