CDKN2A mutations in Spanish cutaneous malignant melanoma families and patients with multiple melanomas and other neoplasia
- Anna Ruiza,
- Susana Puigb,
- Josep Malvehyb,
- Conxi Lázaroa,
- Michael Lyncha,
- Anna M Gimenez-Arnauc,
- Lluis Puigd,
- Julian Sánchez-Conejoe,
- Xavier Estivilla,
- Teresa Castelb
- aMedical and Molecular Genetics Centre-IRO, Hospital Duran i Reynals, Avia Castelldefels, Km 2.7, L’Hospitalet de Llobregat, 08907 Barcelona, Catalonia, Spain, bDermatology Service, Hospital Clínic, Barcelona, Catalonia, Spain, cDermatology Service, Hospital del Mar, Barcelona, Catalonia, Spain, dDermatology Service, Hospital de Sant Pau, Barcelona, Catalonia, Spain, eDermatology Service, Hospital Virgen del Rocio, Sevilla, Spain
- Dr Estivill.
- Received 5 August 1998
- Revised 28 January 1999
Abstract
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 1β 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.
