BRCA1, BRCA2, TP53, and CDKN2A germline mutations in patients with breast cancer and cutaneous melanoma

Familial Cancer (2007) 6:453461

DOI 10.1007/s10689-007-9143-y

Christian Monnerat Agns Chompret Caroline Kannengiesser Marie-Franoise Avril Nicolas Janin Alain Spatz Jean-Marc Guinebretire Catalin Marian Michel Barrois Franoise Boitier Gilbert M. Lenoir Brigitte Bressac-de Paillerets

Received: 21 February 2007 / Accepted: 14 May 2007 / Published online: 12 July 2007 Springer Science+Business Media B.V. 2007

Abstract

Purpose From epidemiological studies it appears that breast cancer (BC) and cutaneous melanoma (CMM) in the same individual occur at a higher frequency than expected by chance. Genetic factors common to both cancers can be

suspected. Our goal was to estimate the involvement of high risk genes in patients presenting these two neoplasia, selected irrespectively from family history and age at diagnosis.Experimental design Eighty two patients with BC andCMM were screened for BRCA1, BRCA2, TP53,CDKN2A and CDK4 (exon 2) germline mutations.Results Deleterious mutations were identied in 6 patients: two carriers of a BRCA1 germline mutation, two carriers of TP53 germline mutations (one of which also harbored a BRCA2 deleterious mutation, the other one aBRCA2 unclassied variant), and two carriers of aCDKN2A germline mutation. In addition, 6 variants of unknown signication were identied in BRCA1 or BRCA2 genes. Regarding family history, 3/13 (23%) patients with a positive family history of BC or CMM were carriers of a germline mutation, whereas only 3/69 (4%) patients without family history were carriers of a germline mutation.Conclusion Our ndings show that few patients with BC and CMM who lacked family histories of these cancers are carriers of deleterious germline mutations in four of the ve genes we examined. We describe for the rst time, two simultaneous BRCA2 and TP53 mutations, suggesting that analysis in more than one gene could be performed if a patients personal or familial history does not match a single syndrome.

Keywords BRCA TP53 CDKN2A Melanoma

Breast cancer

Introduction

While many cases of multiple primary cancers occurring in a same individual are due to a few well characterized

BRCA1, BRCA2, TP53, and CDKN2A germline mutations in patients with breast cancer and cutaneous melanoma

C. Monnerat C. Kannengiesser C. Marian M. Barrois G. M. Lenoir B. Bressac-de Paillerets (&) Department of Genetics, Institut Gustave Roussy, 39 rue Camille Desmoulins, Villejuif Cedex 94805, Francee-mail: [email protected]

A. Chompret

Oncological Genetics, Department of Medicine, Institut Gustave Roussy, Villejuif...