Ovarian cancer: loss of heterozygosity frequently occurs in the ATM gene, but structural alterations do not occur in this gene.

Ataxia-telangiectasia is a multisystem recessive disease characterized clinically by cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency, sensitivity to radiomimetic agents and an increased predisposition to cancer. This pleiotropic disorder is caused by mutations in the ATM gene, which is located at the human chromosomal region 11q23. Loss of heterozygosity (LOH) at 11q22-q23 is a frequent event in ovarian cancer, suggesting the presence of a tumor suppressor gene in this region. We have found that LOH in the ATM gene occurred in 44% of informative cases in a series of 22 primary ovarian tumors. LOH of this region occurred at the same frequency during the advanced stages (III-IV; 3/9, 33%) as in the early stages (I-II; 4/13, 31%) of ovarian cancer. To investigate the role of ATM in ovarian cancer, we used a PCR-based single-strand conformation polymorphism assay for mutation detection of the entire coding sequence of the ATM gene (65 exons) in 22 ovarian tumors. No somatic alterations of the ATM gene were found in these ovarian cancer samples including those with LOH present in the ATM gene. Our study has identified a region (11q23) which probably contains a frequently altered tumor suppressor gene in ovarian cancer, and this gene does not appear to involve the coding sequences of the ATM gene.