Sporadic multiple primary melanoma cases: CDKN2A germline mutations with a founder effect
Stéphane Auroy
Service de Génétique, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorMarie-Françoise Avril
Service de Dermatologie, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorAgnès Chompret
Service de Dermatologie, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorDanièle Pham
Service de Génétique, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorAlisa M. Goldstein
Genetic Epidemiology Branch, National Cancer Institute, Bethesda, Maryland
Search for more papers by this authorGiovanna Bianchi-Scarrà
Department of Oncology, Biology and Genetics, University of Genova, Genova, Italy
Search for more papers by this authorThierry Frebourg
INSERM EPI9906, Faculté de Médecine et de Pharmacie, IFMRP, Rouen, France
Search for more papers by this authorPascal Joly
Service de Dermatologie, Centre Hospitalo-Universitaire Charles Nicolle, Rouen, France
Search for more papers by this authorAlain Spatz
Département d'Anatomopathologie, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorCarole Rubino
Service de Génétique, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorFlorence Demenais
INSERM EPI 00-06, Génétique des Maladies Humaines, Hôpital Saint-Louis, Paris, France
Search for more papers by this authorFrench Hereditary Melanoma Study Group
The members of the French Hereditary Melanoma Study Group for this work included F. Berard, J.F. Blanc, F. Boitier, J.M. Bonnetblanc, F. Caux, J.P. Cesarini, J. Chevrant-Breton, L. Demange, E. Esteve, M. Frenay, F. Grange, B. Guillot, M. d'Incan, C. Lasset, C. Le Corvaisier-Pieto, M. Longy, J.L. Michel, P. Saiag, B. Sassolas, R. Triller, and P. Vabres.
Search for more papers by this authorCorresponding Author
Brigitte Bressac-de Paillerets
Service de Génétique, Institut Gustave Roussy, Villejuif, France
Service de Génétique, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, FranceSearch for more papers by this authorStéphane Auroy
Service de Génétique, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorMarie-Françoise Avril
Service de Dermatologie, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorAgnès Chompret
Service de Dermatologie, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorDanièle Pham
Service de Génétique, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorAlisa M. Goldstein
Genetic Epidemiology Branch, National Cancer Institute, Bethesda, Maryland
Search for more papers by this authorGiovanna Bianchi-Scarrà
Department of Oncology, Biology and Genetics, University of Genova, Genova, Italy
Search for more papers by this authorThierry Frebourg
INSERM EPI9906, Faculté de Médecine et de Pharmacie, IFMRP, Rouen, France
Search for more papers by this authorPascal Joly
Service de Dermatologie, Centre Hospitalo-Universitaire Charles Nicolle, Rouen, France
Search for more papers by this authorAlain Spatz
Département d'Anatomopathologie, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorCarole Rubino
Service de Génétique, Institut Gustave Roussy, Villejuif, France
Search for more papers by this authorFlorence Demenais
INSERM EPI 00-06, Génétique des Maladies Humaines, Hôpital Saint-Louis, Paris, France
Search for more papers by this authorFrench Hereditary Melanoma Study Group
The members of the French Hereditary Melanoma Study Group for this work included F. Berard, J.F. Blanc, F. Boitier, J.M. Bonnetblanc, F. Caux, J.P. Cesarini, J. Chevrant-Breton, L. Demange, E. Esteve, M. Frenay, F. Grange, B. Guillot, M. d'Incan, C. Lasset, C. Le Corvaisier-Pieto, M. Longy, J.L. Michel, P. Saiag, B. Sassolas, R. Triller, and P. Vabres.
Search for more papers by this authorCorresponding Author
Brigitte Bressac-de Paillerets
Service de Génétique, Institut Gustave Roussy, Villejuif, France
Service de Génétique, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, FranceSearch for more papers by this authorAbstract
Multiple primary cancers are one of the hallmarks of inherited predisposition. Outside the familial context, multiple primary tumors could be related either to germline de novo mutations or to low-penetrance mutations, in predisposing genes. We selected 100 patients who displayed multiple primary melanoma (MPM) without any known melanoma cases recorded within their families and looked for germline mutations in the two melanoma-predisposing genes identified to date, CDKN2A and CDK4 exon 2. Nine patients (9%) had germline mutations in CDKN2A, whereas none carried germline mutations in exon 2 of CDK4. Seven cases displayed a recurrent missense mutation, G101W, already described in more than 20 melanoma-prone families; one case carried a missense mutation never reported to date (P114S), and the last case was a carrier of a 6 bp insertion at nucleotide 57 resulting in a duplication of codons 18 and 19. To ascertain whether the G101W was a mutational hot spot for de novo mutations or a common founder mutation, we genotyped eight microsatellite markers flanking the CDKN2A gene. After allowing for recombination over time, haplotype sharing provided evidence for an original G101W mutation common to 6 out of 7 sporadic MPM cases. Therefore, it can be concluded that de novo germline CDKN2A mutations associated with MPM are rare. © 2001 Wiley-Liss, Inc.
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