title: A Ser49Cys variant in the ataxia telangiectasia, mutated, gene that is more common in patients with breast carcinoma compared with population controls.
abstract: BACKGROUND
  Mothers of children who have ataxia telangiectasia have been reported to be at increased risk for development of breast carcinoma. To test whether sequence variants in the ataxia telangiectasia, mutated, gene (ATM) are associated with breast carcinoma, the authors compared the frequency of ATM cDNA sequence changes in patients with breast carcinoma with the corresponding frequency in control patients.
  
  
  METHODS
  The authors sequenced ATM cDNA from 91 patients with breast carcinoma and compared the frequencies of sequence changes in these patients with the corresponding frequencies in a control sample of 940 individuals with no history of malignant disease.
  
  
  RESULTS
  Thirty-five patients with breast carcinoma had one or more single-base changes in ATM. Three genetic variants were found in at least two patients. These variants resulted in Asp1853Asn, Pro1054Arg, or Ser49Cys amino acid substitutions in the ATM protein. The Ser49Cys variant was more common in patients with breast carcinoma than in the control patients, with respective frequencies of 6.7% (5 of 75 patients) and 1.3% (12 of 940 patients; P=0.006; Fisher two-sided exact test). The subgroup of patients with bilateral breast carcinoma had a Ser49Cys frequency of 11.8% (2 of 17 patients), which again was significantly different from what was observed in the control group (P=0.024; Fisher two-sided exact test). The allele frequencies of the other two variants were not different between case patients and control patients.
  
  
  CONCLUSIONS
  Patients with breast carcinoma, particularly those with bilateral disease, were more likely to have a variant in the ATM gene that resulted in a Ser49Cys substitution in the gene product. Additional studies are needed to evaluate the potential functional consequences of the Ser49Cys substitution and confirm the relevance of this variant in the development of breast carcinoma.
authors.affiliation: Department of Radiation Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA. tbuchhol@mdanderson.org
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchholz
authors.forename: Michael M
authors.initials: MM
authors.lastname: Weil
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Ashorn
authors.forename: Eric A
authors.initials: EA
authors.lastname: Strom
authors.forename: Alice
authors.initials: A
authors.lastname: Sigurdson
authors.forename: Melissa
authors.initials: M
authors.lastname: Bondy
authors.forename: Ranajit
authors.initials: R
authors.lastname: Chakraborty
authors.forename: James D
authors.initials: JD
authors.lastname: Cox
authors.forename: Marsha D
authors.initials: MD
authors.lastname: McNeese
authors.forename: Michael D
authors.initials: MD
authors.lastname: Story
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics*; D001260:Ataxia Telangiectasia / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases