title: Identification of point mutations and large rearrangements in the BRCA1 gene in 667 Turkish unselected ovarian cancer patients.
abstract: OBJECTIVE
  The aim of this study was to evaluate the prevalence and spectrum of a known founder mutation, 5382insC and large genomic rearrangements (LGRs) in BRCA1 in ovarian cancer patients in Turkey. The additional aim was to determine the genetic testing strategy in Turkish breast/ovarian cancer family.
  
  
  METHODS
  Six hundred and sixty-seven ovarian cancer patients from five large geographical regions in Turkey, 61 of which had family history of breast/ovarian cancer, were tested for the mutation 5382insC by mutagenically separated polymerase chain reaction and direct sequencing of the entire coding sequence and the splicing sites. Additionally, multiplex ligation-dependent probe amplification (MLPA) was performed for large mutational scanning of BRCA1 gene in unselected ovarian cancer.
  
  
  RESULTS
  In this study, BRCA1 point mutations were observed in 1% of all patients and 9.8% of familial cases: 5382insC, unique novel missense variant-G1748S and unclassified splice site variant IVS20+5A>T. 5382insC was observed in two patients. However, G1748S, previously unreported, was found in four patients and thus led to the conclusion that this mutation may be unique to Turkey. A splice site variant, IVS20+5A>T, was detected in three patients, with two of them including G1748S and IVS20+5A>T, together. Using MLPA, six different distinct LGRs in BRCA1 were observed: the deletion of E1A-1B-2, E11, E17-19, E18 and E18-19 and duplication of E5-9. The prevalence of LGRs in this study was 40.9% among patients with family history. The deletion of E1A-1B-2 was the common mutation, and patients with this deletion were referred to us from four different geographical regions in Turkey. Therefore, it was hypothesized that this deletion covering E1-2 is common in Turkey.
  
  
  CONCLUSIONS
  LGRs in BRCA1 were strongly associated with positive family history among the Turkish population. On the basis of these findings, it can be recommended that a low-cost screening for LGRs in BRCA1 may be the first-line mutation detection method in families with strong breast/ovarian cancer history in Turkey.
authors.affiliation: Department of Genetics, Hacettepe University Medical School, Ankara, Turkey. daktas@hacettepe.edu.tr
authors.forename: D
authors.initials: D
authors.lastname: Aktas
authors.forename: M
authors.initials: M
authors.lastname: Gultekin
authors.forename: S
authors.initials: S
authors.lastname: Kabacam
authors.forename: M
authors.initials: M
authors.lastname: Alikasifoglu
authors.forename: A T
authors.initials: AT
authors.lastname: Turan
authors.forename: G
authors.initials: G
authors.lastname: Tulunay
authors.forename: M F
authors.initials: MF
authors.lastname: Kose
authors.forename: F
authors.initials: F
authors.lastname: Ortac
authors.forename: K
authors.initials: K
authors.lastname: Yüce
authors.forename: E
authors.initials: E
authors.lastname: Tunçbilek
authors.forename: A
authors.initials: A
authors.lastname: Ayhan
mesh_terms: D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D019398:Genes, BRCA1; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics*; D017354:Point Mutation; D014421:Turkey
chemical_list: D004273:DNA, Neoplasm