title: A novel BRCA2 in frame deletion in a Tunisian woman with early onset sporadic breast cancer.
abstract: BACKGROUND
  Breast cancer is increasing among young women in Tunisia. Germline mutations in the BRCA1/2 genes are associated with a high risk for breast cancer development. However, the true contribution of BRCA1/2 mutation in sporadic breast cancer is not well documented. Our aim is to identify the BRCA2 mutation spectrum in Tunisian young women with breast cancer.
  
  
  METHODS
  Screening the BRCA2 gene was performed using DHPLC, DNA sequencing and PCR-RFLP.
  
  
  RESULTS
  We identified, in a woman diagnosed with early onset breast cancer, and without family history, a novel in frame deletion 5456delGTAGCA in the exon 11 of the BRCA2 gene which causes a loss of two residues Ser1743-Ser1744. The absence of this deletion in the patients' parents suggests that it is a de novo variant. Furthermore, we screened 108 sporadic cases, 50 familial cases, and 60 controls for the identified del6bp using PCR-RFLP. None of them carried this deletion suggesting that this variant is not a benign polymorphism and probably rare in our population. With regards to the position of the Ser1743-1744 in the BRCT domain, sequence alignment revealed that the Ser1743 is conserved among several species, which may reflect its importance in the BRCA2 function. A modeling of the wild-type and mutated BRC5-BRC6 domain revealed that the deletion of the 2 Serine residues might affect the structure of this BRCA2 domain.
  
  
  CONCLUSIONS
  A novel in frame deletion 5456del6bp in BRCA2 gene was identified in an early onset woman with breast cancer and without family history.
authors: Center of Biotechnology of Sfax, University of Sfax, BP K 3018, Sfax, Tunisia.
authors: N
authors: N
authors: Hadiji-Abbes
authors: Center of Biotechnology of Sfax, University of Sfax, BP K 3018, Sfax, Tunisia.
authors: F
authors: F
authors: Trifa
authors: Center of Biotechnology of Sfax, University of Sfax, BP K 3018, Sfax, Tunisia.
authors: M
authors: M
authors: Choura
authors: Departement of Anatomoapathology, Oncology and Radiotherapy of Habib Bourguiba Hospital, Sfax, Tunisia.
authors: A
authors: A
authors: Khabir
authors: Departement of Anatomoapathology, Oncology and Radiotherapy of Habib Bourguiba Hospital, Sfax, Tunisia.
authors: T
authors: T
authors: Sellami-Boudawara
authors: Departement of Anatomoapathology, Oncology and Radiotherapy of Habib Bourguiba Hospital, Sfax, Tunisia.
authors: M
authors: M
authors: Frikha
authors: Departement of Anatomoapathology, Oncology and Radiotherapy of Habib Bourguiba Hospital, Sfax, Tunisia.
authors: J
authors: J
authors: Daoud
authors: Center of Biotechnology of Sfax, University of Sfax, BP K 3018, Sfax, Tunisia. Electronic address: raja.gargouri@cbs.rnrt.tn.
authors: R
authors: R
authors: Mokdad-Gargouri
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D024682:BRCA2 Protein / Q000737:chemistry / Q000502:physiology; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D017124:Conserved Sequence; D005091:Exons / Q000235:genetics; D005260:Female; D024522:Genes, BRCA2; D005820:Genetic Testing; D006801:Humans; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016364:Reading Frames / Q000235:genetics; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000737:chemistry; D013045:Species Specificity; D014416:Tunisia / Q000453:epidemiology; D055815:Young Adult
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D009363:Neoplasm Proteins; D012694:Serine
keywords: BRCA2; Cancer du sein sporadique; Délétion en phase; In frame deletion; Mutation screening; Recherche de mutation; Sporadic breast cancer