title: BRCA1 mutations in women with familial or early-onset breast cancer and BRCA2 mutations in familial cancer in Estonia.
abstract: BACKGROUND
  The aim of this study was to identify BRCA1 and BRCA2 mutations in the Estonian population. We analyzed genetic data and questionnaire from 64 early-onset (< 45 y) breast cancer patients, 47 familial cases (patients with breast or ovarian cancer and a case of these cancers in the family), and 33 predictive cases (patients without breast or ovarian cancer, with a family history of such diseases) from Estonia for mutations in the BRCA1 gene. A sub-set of familial cases and predictive cases were also analyzed for mutations in the BRCA2 gene.
  
  
  METHODS
  For mutation detection, we used the Polymerase Chain Reaction-Single Stranded Conformation Polymorphism Heteroduplex Analysis (PCR-SSCP-HD), followed by direct DNA sequencing.
  
  
  RESULTS
  We identified three clinically important mutations in the BRCA1 gene, including seven occurrences of the c.5382insC mutation, three of c.4154delA, and one instance of c.3881_3882delGA. We also detected six polymorphisms: c.2430T>C, c.3232A>G, c.4158A>G, c.4427T>C, c.4956A>G, and c.5002T>C. Four sequence alterations were detected in introns: c.560+64delT, c.560+ [36-38delCTT, 52-63del12], c.666-58delT, and c.5396+60insGTATTCCACTCC. In the BRCA2 gene, two clinically important mutations were found: c.9610C>T and c.6631delTTAAATG. Additionally, two alterations (c.7049G>T and c.7069+80delTTAG) with unknown clinical significance were detected.
  
  
  CONCLUSIONS
  In our dataset, the overall frequency of clinically important BRCA1 mutations in early-onset patients, familial cases, and predictive testing was 7.6% (144 cases, 11 mutation carriers). Pathogenic mutations were identified in 4 of the 64 early-onset breast cancer cases (6.3%). In familial cases, clinically important mutations in the BRCA1 gene were found in 6 of the 47 individuals analyzed (12.8%). In predictive cases, 1 clinically important mutation was detected in 33 individuals studied (3%). The occurrence of clinically important mutations in BRCA2 in familial cases of breast cancer was 2 of the 16 individuals analyzed (12.5%).
authors.affiliation: National Institute for Health Development, Tallinn, Estonia.|North Estonia Medical Centre, Diagnostics Division, Tallinn, Estonia.
authors.forename: Kristiina
authors.initials: K
authors.lastname: Tamboom
authors.affiliation: Institute of Molecular and Cell Biology of the University of Tartu, Tartu, Estonia.|Department of Neurology, UCSF, CA 94158-2324, USA.
authors.forename: Krista
authors.initials: K
authors.lastname: Kaasik
authors.affiliation: National Institute for Health Development, Tallinn, Estonia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Aršavskaja
authors.affiliation: National Institute for Health Development, Tallinn, Estonia.
authors.forename: Mare
authors.initials: M
authors.lastname: Tekkel
authors.affiliation: National Institute for Health Development, Tallinn, Estonia.|North Estonia Medical Centre, Diagnostics Division, Tallinn, Estonia.
authors.forename: Aili
authors.initials: A
authors.lastname: Lilleorg
authors.affiliation: Clinic of the Hematology and Oncology, Tartu University Hospital, Tartu, Estonia.
authors.forename: Peeter
authors.initials: P
authors.lastname: Padrik
authors.affiliation: Institute of Molecular and Cell Biology of the University of Tartu, Tartu, Estonia.|Estonian Biocentre, Tartu, Estonia.|The Estonian Genome Center of the University of Tartu, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.affiliation: National Institute for Health Development, Tallinn, Estonia.
authors.forename: Toomas
authors.initials: T
authors.lastname: Veidebaum