title: [The clinical importance of a genetic analysis of moderate-risk cancer susceptibility genes in breast and other cancer patients from the Czech Republic].
abstract: BACKGROUND
  Analysis of the major breast cancer (BC) predisposition genes BRCA1 and BRCA2 enables identification of high-risk individuals. Specialized programs enrolling the carriers of BRCA1/2 mutations facilitate an improvement in prevention and early diagnostics in asymptomatic individuals and rationalize the selection of individualized treatment in case of a BC onset. However, the carriers of mutations in the major predisposition genes represent only approximately 25% of cases among high-risk BC patients. Numerous candidate predisposing genes for breast and other cancers have recently been identified. The risk of cancer development associated with alterations in these genes is lower, and there is a considerable population variability in different regions worldwide.
  
  
  OBJECTIVE
  We have performed mutation analyses of moderate-risk cancer susceptibility genes to evaluate their clinical importance for genetic counseling in high-risk patients suffering from breast and other cancers in the Czech population.
  
  
  RESULTS
  Czech oncological patients were analysed for mutation in ATM, CHEK2, NBS1 (NBN) and PALB2 genes. The majority of analyzed individuals represent the population of high-risk BRCA1/2-negative BC patients.
  
  
  CONCLUSIONS
  Based on results of this study, we recommend an analysis of recurrent truncating mutations in the CHEK2 gene (the c.1100delC mutation and a large deletion affecting exons 9-10) in BRCA1/2-negative patients from high-risk BC families. A clinical assessment of missense variants in CHEK2 is not suitable. A routine mutation analysis of the ATM and NBS1 (NBN) genes is not recommended in BC patients due to the low frequency of alterations in these genes in the Czech Republic. An identification of truncating mutations in the PALB2 gene is important in BRCA1/2-negative BC patients from families with a strong history of BC (HBC families). The frequency of PALB2 mutations may be comparable to the frequency of mutations in the BRCA2 gene in Czech HBC families.
authors.affiliation: Ústav biochemie a experimentální onkologie, 1. LF UK a VFN v Praze. ppohl@lf1.cuni.cz
authors.forename: P
authors.initials: P
authors.lastname: Pohlreich
authors.forename: Z
authors.initials: Z
authors.lastname: Kleibl
authors.forename: P
authors.initials: P
authors.lastname: Kleiblová
authors.forename: M
authors.initials: M
authors.lastname: Janatová
authors.forename: J
authors.initials: J
authors.lastname: Soukupová
authors.forename: E
authors.initials: E
authors.lastname: Macháčková
authors.forename: J
authors.initials: J
authors.lastname: Házová
authors.forename: P
authors.initials: P
authors.lastname: Vašíčková
authors.forename: E
authors.initials: E
authors.lastname: Sťahlová Hrabincová
authors.forename: M
authors.initials: M
authors.lastname: Navrátilová
authors.forename: M
authors.initials: M
authors.lastname: Svoboda
authors.forename: L
authors.initials: L
authors.lastname: Foretová
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics; D064447:Checkpoint Kinase 2; D004268:DNA-Binding Proteins / Q000235:genetics; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D000076164:Fanconi Anemia Complementation Group N Protein; C112156:NBN protein, human; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins; D064447:Checkpoint Kinase 2; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases