The contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma

F. Lesueur, M. De Lichy, M. Barrois, G. Durand, J. Bombled, M. F. Avril, A. Chompret, F. Boitier, G. M. Lenoir, B. Bressac-de Paillerets*, Monique Baccard, Bertrand Bachollet, Pascaline Berthet, Valérie Bonadona, Jean Marie Bonnetblanc, Olivier Caron, Jacqueline Chevrant-Breton, Jean François Cuny, Stéphane Dalle, Michèle DelaunayLiliane Demange, Julie De Quatrebarbes, Jean François Doré, Marc Frénay, Jean Pierre Fricker, Marion Gauthier-Villars, Paul Gesta, Sophie Giraud, Philippe Gorry, Florent Grange, Andrew Green, Laetitia Huiart, Nicolas Janin, Pascal Joly, Delphine Kérob, Christine Lasset, Dominique Leroux, Jean Marc Limacher, Michel Longy, Sandrine Mansard, Karine Marrou, Tanguy Martin-Denavit, Christine Mateus, Eve Maubec, Laurence Olivier-Faivre, Vincent Orlandini, Pascal Pujol, Bruno Sassolas, Dominique Stoppa-Lyonnet, Luc Thomas, Pierre Vabres, Laurence Venat, Ewa Wierzbicka, Hélène Zattara

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

24 Citations (Scopus)


Mutations in two genes encoding cell cycle regulatory proteins have been shown to cause familial cutaneous malignant melanoma (CMM). About 20% of melanoma-prone families bear a point mutation in the CDKN2A locus at 9p21, which encodes two unrelated proteins, p16INK4a and p14ARF. Rare mutations in CDK4 have also been linked to the disease. Although the CDKN2A gene has been shown to be the major melanoma predisposing gene, there remains a significant proportion of melanoma kindreds linked to 9p21 in which germline mutations of CDKN2A have not been identified through direct exon sequencing. The purpose of this study was to assess the contribution of large rearrangements in CDKN2A to the disease in melanoma-prone families using multiplex ligation-dependent probe amplification. We examined 214 patients from independent pedigrees with at least two CMM cases. All had been tested for CDKN2A and CDK4 point mutation, and 47 were found positive. Among the remaining 167 negative patients, one carried a novel genomic deletion of CDKN2A exon 2. Overall, genomic deletions represented 2.1% of total mutations in this series (1 of 48), confirming that they explain a very small proportion of CMM susceptibility. In addition, we excluded a new gene on 9p21, KLHL9, as being a major CMM gene.

Original languageEnglish
Pages (from-to)364-370
Number of pages7
JournalBritish Journal of Cancer
Issue number2
Publication statusPublished - 22 Jul 2008


  • CDKN2A
  • KLHL9
  • Melanoma-prone families
  • Multiplex ligation-dependent probe amplification
  • p14
  • p16


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