title: Absence of somatic ATM missense mutations in 58 mammary carcinomas.
abstract: Accumulating evidence indicates that germline missense mutations in the ATM gene predispose to breast cancer. To investigate the potential role of somatic ATM mutations in the tumorigenesis of breast cancer, the ATM gene was scanned in 58 mammary carcinomas using DOVAM-S (detection of virtually all mutations-SSCP [single-strand conformation polymorphism]), a robotically enhanced, highly redundant form of SSCP that detects virtually all mutations. A total of 1.65 megabases of tumor DNA sequence was scanned and 16 structural variants were identified, including one novel nonsense mutation, four novel missense mutations, and a common missense change in African-Americans. Sequencing from microdissected normal cells reveals that all variants were present in the germline. Thus, the ATM gene may be similar to the BRCA1/BRCA2 genes in that germline mutations are important in cancer predisposition, but somatic mutations are seldom present in tumors. Loss of heterozygosity (LOH) is common in these tumors, but ATM missense mutations occur with similar frequencies when LOH is present or absent (P=0.73). If germline ATM missense mutations predispose to breast cancer, the unmasking of a recessive missense allele by LOH does not seem to be a critical step in breast neoplasia.
authors.affiliation: Department of Molecular Genetics, City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Jinong
authors.initials: J
authors.lastname: Feng
authors.forename: Jin
authors.initials: J
authors.lastname: Yan
authors.forename: Jiesheng
authors.initials: J
authors.lastname: Chen
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schlake
authors.forename: Zefei
authors.initials: Z
authors.lastname: Jiang
authors.forename: Carolyn H
authors.initials: CH
authors.lastname: Buzin
authors.forename: Steve S
authors.initials: SS
authors.lastname: Sommer
authors.forename: Anatoly
authors.initials: A
authors.lastname: Dritschilo
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics*; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D020125:Mutation, Missense; 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