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

Fabienne Lesueur 1 Mahaut de Lichy 2 Michel Barrois 3 Guillermo Durand 4 Johny Bombled 5 Marie-Francoise Avril 6 Agnès Chompret 7 Françoise Boitier Gilbert M Lenoir 8 Monique Baccard 9 Bertrand Bachollet Pascaline Berthet 10 Valérie Bonadona Jean-Marie Bonnetblanc 11 Jacqueline Chevrant-Breton 12 Jean-Francois Cuny, 13 Stéphane Dalle 14 Michèle Delaunay Liliane Demange Julie De Quatrebarbes 15 Jean-François Doré 16 Marc Frénay Jean-Pierre Fricker Marion Gauthier-Villars Paul Gesta Sophie Giraud Philippe Gorry 17 Florent Grange 18 Andrew Green Laetitia Huiart 19 Nicolas Janin Pascal Joly Delphine Kerob Christine Lasset 20 Dominique Leroux Jean-Marc Limacher 21 Michel Longy Sandrine Mansard 22 Karine Marrou Tanguy Martin-Denavit Christine Mateus 23 Eve Maubec 24 Laurence Olivier-Faivre 25 Vincent Orlandini Pascal Pujol 26 Bruno Sassolas 27 Dominique Stoppa-Lyonnet 28 Luc Thomas Pierre Vabres 29 Laurence Venat Ewa Wierzbicka Helene Zattara Brigitte Bressac-de Paillerets 2 
4 Service de Génétique [Villejuif]
IGR - Institut Gustave Roussy
20 Biostatistiques santé
Département biostatistiques et modélisation pour la santé et l'environnement [LBBE]
23 Service de dermatologie
Département de médecine oncologique [Gustave Roussy]
Abstract : 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, p16(INK4a) and p14(ARF). 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.
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Submitted on : Thursday, June 2, 2022 - 3:22:14 PM
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Fabienne Lesueur, Mahaut de Lichy, Michel Barrois, Guillermo Durand, Johny Bombled, et al.. The contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma. British Journal of Cancer, Cancer Research UK, 2008, 99 (2), pp.364-370. ⟨10.1038/sj.bjc.6604470⟩. ⟨hal-02196212⟩



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