title: ATM gene mutations in sporadic breast cancer patients from Brazil.
abstract: OBJECTIVE
  The Ataxia-telangiectasia mutated (ATM) gene encodes a multifunctional kinase, which is linked to important cellular functions. Women heterozygous for ATM mutations have an estimated relative risk of developing breast cancer of 3.8. However, the pattern of ATM mutations and their role in breast cancer etiology has been controversial and remains unclear. In the present study, we investigated the frequency and spectrum of ATM mutations in a series of sporadic breast cancers and controls from the Brazilian population.
  
  
  METHODS
  Using PCR-Single Strand Conformation Polymorphism (SSCP) analysis and direct DNA sequencing, we screened a panel of 100 consecutive, unselected sporadic breast tumors and 100 matched controls for all 62 coding exons and flanking introns of the ATM gene.
  
  
  RESULTS
  Several polymorphisms were detected in 12 of the 62 coding exons of the ATM gene. These polymorphisms were observed in both breast cancer patients and the control population. In addition, evidence of potential ATM mutations was observed in 7 of the 100 breast cancer cases analyzed. These potential mutations included six missense variants found in exon 13 (p.L546V), exon 14 (p.P604S), exon 20 (p.T935R), exon 42 (p.G2023R), exon 49 (p.L2307F), and exon 50 (p.L2332P) and one nonsense mutation in exon 39 (p.R1882X), which was predicted to generate a truncated protein.
  
  
  CONCLUSIONS
  Our results corroborate the hypothesis that sporadic breast tumors may occur in carriers of low penetrance ATM mutant alleles and these mutations confer different levels of breast cancer risk.
authors.affiliation: Laboratory of Molecular Genetics, Center for Translational Research in Oncology, Av Dr Arnaldo, 251, 8th Floor, CEP 01246-000 São Paulo, Brazil.
authors.forename: Flavia Rotea
authors.initials: FR
authors.lastname: Mangone
authors.affiliation: Laboratory of Molecular Genetics, Center for Translational Research in Oncology, Av Dr Arnaldo, 251, 8th Floor, CEP 01246-000 São Paulo, Brazil.
authors.forename: Elisabete C
authors.initials: EC
authors.lastname: Miracca
authors.affiliation: Department of Pathology and Molecular Medicine, Richardson Laboratory, Queen's University, 88 Stuart Street, Kingston, Ontario K7L 3N6 Canada.
authors.forename: Harriet E
authors.initials: HE
authors.lastname: Feilotter
authors.affiliation: Department of Pathology and Molecular Medicine, Cancer Research Institute, Queen's University, Botterell Hall, 10 Stuart Street, Kingston, Ontario K7L 3N6 Canada.
authors.forename: Lois M
authors.initials: LM
authors.lastname: Mulligan
authors.affiliation: Laboratory of Molecular Genetics, Center for Translational Research in Oncology, Av Dr Arnaldo, 251, 8th Floor, CEP 01246-000 São Paulo, Brazil ; Discipline of Oncology, Department of Radiology and Oncology, Faculty of Medicine, University of São Paulo, Av Dr Arnaldo, 455, 4th Floor, CEP 01246-903 São Paulo, Brazil.
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: Nagai
keywords: ATM gene; Breast cancer; Mutations; Polymorphisms