title: Screening for common mutations in BRCA1 and BRCA2 genes: interest in genetic testing of Tunisian families with breast and/or ovarian cancer.
abstract: BACKGROUND
  In the Tunisian population, as yet a limited number of BRCA1/2 germline mutations have been reported in hereditary breast and/or ovarian cancer. These mutations are located in a few exons of BRCA1/2. The aim of the present study was to search for these mutations in 66 unrelated patients with hereditary breast and/or ovarian cancer in order to assess the interest in such a targeted approach for genetic testing in Tunisia.
  
  
  METHODS
  Blood specimens from the 66 Tunisian patients, with family history of breast and/or ovarian cancer, were collected at the Salah Azaiz Cancer Institute of Tunis. The exons 5, 20 and part of exon 11 of BRCA1 as well as part of exons 10 and 11 of BRCA2 were analyzed by Sanger sequencing.
  
  
  RESULTS
  12 patients had deleterious mutations in the BRCA1 or BRCA2 genes (18%), including a novel frame-shift mutation of BRCA1 (c.3751dup; 3780insT). Four distinct BRCA1 mutations were detected eight patients: c.5266dup (5382insC) and c.211dup (330insA) each in three patients, c.3751dup (3870insT) and c.4041_4042del (4160delAG) each in one patient. The four remaining cases all carried the same BRCA2 mutation, c.1310_1313del (1538delAAGA). Besides these deleterious mutations, eight polymorphisms and unclassified variants were detected, one of them being never reported (BRCA1c.3030T>G, p.Pro1010Pro).
  
  
  CONCLUSIONS
  In this study, we show that targeting relevant exons in BRCA1 and BRCA2 genes allows detection of a substantial percentage of mutations in the Tunisian population. Therefore such an approach may be of interest in genetic testing of high-risk breast and ovarian cancer families in Tunisia.
authors.affiliation: Institut Salah Azaiz Cancer, Department of Immuno-Histo-Cytology, place Bab-Saadoun, 1006 Tunis, Tunisia.
authors.forename: Asma
authors.initials: A
authors.lastname: Fourati
authors.affiliation: Oscar Lambret Cancer Centre, Laboratory of Human Molecular Biology, Lille, France.
authors.forename: Marie-Michèle
authors.initials: MM
authors.lastname: Louchez
authors.affiliation: Oscar Lambret Cancer Centre, Laboratory of Human Molecular Biology, Lille, France.
authors.forename: Joelle
authors.initials: J
authors.lastname: Fournier
authors.affiliation: Institut Salah Azaiz Cancer, Department of Immuno-Histo-Cytology, place Bab-Saadoun, 1006 Tunis, Tunisia.
authors.forename: Amor
authors.initials: A
authors.lastname: Gamoudi
authors.affiliation: Salah Azaiz Cancer Institute, Department of Surgery, Tunis, Tunisia.
authors.forename: Khaled
authors.initials: K
authors.lastname: Rahal
authors.affiliation: Institut Salah Azaiz Cancer, Department of Immuno-Histo-Cytology, place Bab-Saadoun, 1006 Tunis, Tunisia.
authors.forename: Michèle-Véronique
authors.initials: MV
authors.lastname: El May
authors.affiliation: Institut Salah Azaiz Cancer, Department of Immuno-Histo-Cytology, place Bab-Saadoun, 1006 Tunis, Tunisia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: El May
authors.affiliation: Oscar Lambret Cancer Centre, Laboratory of Human Molecular Biology, Lille, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Revillion
authors.affiliation: Oscar Lambret Cancer Centre, Laboratory of Human Molecular Biology, Lille, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Peyrat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D005091:Exons; D005192:Family Health; D005260:Female; D016368:Frameshift Mutation; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D064726:Triple Negative Breast Neoplasms / Q000235:genetics; D014416:Tunisia; D055815:Young Adult
keywords: BRCA1; BRCA2; Tunisia; genetic testing; hereditary breast and ovarian cancer; targeted approach