title: Mutations of the BRCA1 gene in hereditary breast and ovarian cancer in the Czech Republic.
abstract: OBJECTIVE
  Mutations in the BRCA1 gene confer a high risk for the development of breast or ovarian cancer. The aim of this study was to establish the frequency and spectrum of BRCA1 mutations in Czech breast or ovarian cancer families.
  
  
  METHODS
  We have screened 28 patients with early-onset cancer and 54 patients from risk families for germ-line mutations in BRCA1. All coding exons were analyzed by the protein truncation test (PTT) and the reverse transcription polymerase chain reaction (RT-PCR). Detected variants were characterized by direct sequencing of PCR products.
  
  
  RESULTS
  Five distinct deleterious mutations have been identified in six families. All the mutations led to the premature termination of translation. One mutation was detected in a group of 11 (9.1%) patients with early-onset breast cancer. Two mutations were observed in 32 (6.3%) families with a history of breast cancer only. Three mutations were found in 22 (13.6%) families with both breast and ovarian cancer. The 5382insC mutation was the only abnormality detected twice. In addition, two variant transcripts, the loss of exon 5 and in-frame 3-bp deletion at the beginning of exon 8, were identified only at the cDNA level. Their biological significance remains unknown.
  
  
  CONCLUSIONS
  PTT analysis enables examination of long PCR products. The technique is useful for rapid detection of mutations in hereditary breast cancer.
authors.affiliation: 2nd Department of Medical Chemistry and Biochemistry, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. ppohl@lfl.cuni.cz
authors.forename: P
authors.initials: P
authors.lastname: Pohlreich
authors.forename: J
authors.initials: J
authors.lastname: Stríbrná
authors.forename: Z
authors.initials: Z
authors.lastname: Kleibl
authors.forename: M
authors.initials: M
authors.lastname: Zikán
authors.forename: R
authors.initials: R
authors.lastname: Kalbácová
authors.forename: L
authors.initials: L
authors.lastname: Petruzelka
authors.forename: B
authors.initials: B
authors.lastname: Konopásek
mesh_terms: D000328:Adult; D017668:Age of Onset; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D018153:Czech Republic / Q000453:epidemiology; D005260:Female; D019398:Genes, BRCA1; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction