title: Elevated frequency of ATM gene missense mutations in breast cancer relative to ethnically matched controls.
abstract: Studies of families of patients with ataxia telangiectasia (A-T) show an increased risk of breast cancer in heterozygous A-T carriers. However, expected increased levels of mutations in the ATM gene among unselected breast cancer patients have not been found to date. Previous methods of mutation detection were biased toward the detection of truncating mutations, and single nucleotide substitutions were likely to have been underreported. In this study, genomic DNA from 43 breast cancer patients and 43 control individuals were scanned for mutations in the entire ATM coding region (exons 4-65) and adjacent intronic splice regions (three megabases total) using detection of virtually all mutation-single-strand conformation polymorphism (SSCP), a modification of SSCP with sufficient redundancy to detect virtually all mutations. Excluding a polymorphism found commonly in cases and controls, there were missense changes in 12 breast cancer patients, one of whom also had a protein truncating mutation, versus six controls (P=0.09). When all structural changes common to the cases and controls were excluded, missense or truncating changes were found in 10 cases compared to two in controls (P=0.013). The background of missense changes in controls is high. There is a trend towards elevation of all structural changes in cases, but the results are not statistically significant. Cohort-specific structural changes are significantly more prevalent in the breast cancer patients. The data are compatible with certain missense mutations in ATM predisposing to breast cancer.
authors: Department of Molecular Genetics, City of Hope National Medical Center, Duarte, CA 91010, USA. ssommerlab@coh.org
authors: Steve S
authors: SS
authors: Sommer
authors: Carolyn H
authors: CH
authors: Buzin
authors: Mira
authors: M
authors: Jung
authors: Jian
authors: J
authors: Zheng
authors: Qiang
authors: Q
authors: Liu
authors: Sook J
authors: SJ
authors: Jeong
authors: Jefferson
authors: J
authors: Moulds
authors: Vu Q
authors: VQ
authors: Nguyen
authors: Jinong
authors: J
authors: Feng
authors: William P
authors: WP
authors: Bennett
authors: Anatoly
authors: A
authors: Dritschilo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases