The ATM gene and susceptibility to breast cancer: Analysis of 38 breast tumors reveals no evidence for mutation

Igor Vořechovský, Debora Rasio, Liping Luo, Carmen Monaco, Lennart Hammarström, A. David, B. Webster, Jan Zaloudik, Giuseppe Barbanti-Brodano, Michael James, Giandomenico Russo, Carlo M. Croce, Massimo Negrini

Research output: Contribution to journalArticlepeer-review


Heterozygosity for ataxia-telangiectasia (A-T), a cancer-prone recessive syndrome, has been associated with an increased risk of breast cancer. The gene for A-T (ATM) is located at chromosomal region 11q22-q23, a region of frequent loss of constitutional heterozygosity in breast and other tumors. Loss of constitutional heterozygosity at 11q22-q23 was found in 47% of informative cases in the series of primary tumors analyzed in this study. To investigate the role of ATM in breast cancer, we have determined the complete genomic organization of the gene, developed an extra-scanning PCR single- strand conformational polymorphism (PCR-SSCP) assay for mutation detection of ATM, and screened 38 consecutive breast tumors for mutations using both genomic DNA- and cDNA-based assays. In addition to common ATM polymorphisms detected both in the coding sequence and in flanking introns, seven unique SSCP alleles were identified in six tumor DNAs. Sequence analysis of these alleles revealed five nucleotide substitutions that were predicted to change the encoded amino acid. However, PCR-SSCP and nucleotide sequencing analysis of the paired blood samples and of an extended sample size of a total of 224 chromosomes indicated that these SSCP patterns represent constitutional rare polymorphisms with a frequency between 0.005 and 0.023. Because the majority of A-T mutations are null mutations and none of the ATM alleles found in breast cancer samples would lead to the truncation of the translation product, we conclude that, in this initial sample of sporadic breast cancer patients, there was no evidence for an increased number of A-T carriers. In addition, because no somatic mutations were found, our study rules out the ATM gene as the frequently altered tumor suppressor gene at 11q23.

Original languageEnglish
Pages (from-to)2726-2732
Number of pages7
JournalCancer Research
Issue number12
Publication statusPublished - Jun 15 1996

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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