title: BRCA1, BRCA2, TP53, and CDKN2A germline mutations in patients with breast cancer and cutaneous melanoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Eighty two patients with BC and CMM were screened for BRCA1, BRCA2, TP53, CDKN2A and CDK4 (exon 2) germline mutations.
  
  
  RESULTS
  Deleterious mutations were identified 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 a BRCA2 unclassified variant), and two carriers of a CDKN2A germline mutation. In addition, 6 variants of unknown signification were identified 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.
  
  
  CONCLUSIONS
  Our findings 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 five genes we examined. We describe for the first time, two simultaneous BRCA2 and TP53 mutations, suggesting that analysis in more than one gene could be performed if a patient's personal or familial history does not match a single syndrome.
authors.affiliation: Department of Genetics, Institut Gustave Roussy, 39 rue Camille Desmoulins, Villejuif Cedex, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Monnerat
authors.forename: Agnès
authors.initials: A
authors.lastname: Chompret
authors.forename: Caroline
authors.initials: C
authors.lastname: Kannengiesser
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Avril
authors.forename: Nicolas
authors.initials: N
authors.lastname: Janin
authors.forename: Alain
authors.initials: A
authors.lastname: Spatz
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Guinebretière
authors.forename: Catalin
authors.initials: C
authors.lastname: Marian
authors.forename: Michel
authors.initials: M
authors.lastname: Barrois
authors.forename: Françoise
authors.initials: F
authors.lastname: Boitier
authors.forename: Gilbert M
authors.initials: GM
authors.lastname: Lenoir
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bressac-de Paillerets
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005260:Female; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D012878:Skin Neoplasms / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53; D051358:Cyclin-Dependent Kinase 4