title: Mutation analysis of the AATF gene in breast cancer families.
abstract: BACKGROUND
  About 5-10% of breast cancer is due to inherited disease predisposition. Many previously identified susceptibility factors are involved in the maintenance of genomic integrity. AATF plays an important role in the regulation of gene transcription and cell proliferation. It induces apoptosis by associating with p53. The checkpoint kinases ATM/ATR and CHEK2 interact with and phosphorylate AATF, enhancing its accumulation and stability. Based on its biological function, and direct interaction with several known breast cancer risk factors, AATF is a good candidate gene for being involved in heritable cancer susceptibility.
  
  
  METHODS
  Here we have screened the entire coding region of AATF in affected index cases from 121 Finnish cancer families for germline defects, using conformation sensitive gel electrophoresis and direct sequencing.
  
  
  RESULTS
  Altogether seven different sequence changes were observed, one missense variant and six intronic ones. Based on the in silico analyses of these sequence alterations, as well as their occurrence in cases and controls, none of them, however, were predicted to be pathogenic.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study reporting the mutation screening of the AATF gene in familial breast cancer cases. No evidence for the association with breast cancer was observed.
authors.affiliation: Laboratory of Cancer Genetics, Oulu University Hospital, P,O, Box 22, FIN-90221 Oulu, Finland. maappi@mail.student.oulu.fi
authors.forename: Maria
authors.initials: M
authors.lastname: Haanpää
authors.forename: Mervi
authors.initials: M
authors.lastname: Reiman
authors.forename: Jenni
authors.initials: J
authors.lastname: Nikkilä
authors.forename: Hannele
authors.initials: H
authors.lastname: Erkko
authors.forename: Katri
authors.initials: K
authors.lastname: Pylkäs
authors.forename: Robert
authors.initials: R
authors.lastname: Winqvist
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000032:analysis / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics*
chemical_list: C402637:AATF protein, human; D051017:Apoptosis Regulatory Proteins; D012097:Repressor Proteins