Low Incidence of Deletions of ATM (ataxia-telangiectasia mutated) Gene in Patients (pts) with Multiple Myeloma (MM) as Detected by FISH.

Loss of function of ATM gene is associated with higher incidence of leukemia and lymphoma. ATM localized to 11q22.3-q23.1, is a tumor suppressor gene and plays an important role in cell cycle arrest, DNA repair mechanisms, and apoptosis. The incidence of deletion of ATM in MM remains unknown. Using a new commercially available fluorescently labeled DNA probe, we investigated the incidence of homozygous and heterozygous deletions of the ATM gene locus to explore its potential role in the pathogenesis of multiple myeloma (MM). Fifty-three MM pts were evaluated by fluorescence in situ hybridization (FISH) using the Vysis, Inc. LSI ATM (11q22.3) probe to assess the status of the ATM gene. LSI ATM (11q22.3) is a ~500 kb probe that hybridizes to the 11q22.3 region of chromosome 11 and spans the entire ~184 kb ataxia telangiectasia mutated (ATM) gene and several others. Probe copy number was assessed in each patient after analyzing at least 200 interphase nuclei. Only pts with> 10% bone marrow involvements with malignant plasma cells were analyzed. Heterozygous ATM deletion was noted in 2/53 (3.7%) patients. These patients had 82% and 20% involvement of bone marrow (BM) with malignant plasma cells. Twenty-eight of 53 (%) patients showed an extra signal suggestive of trisomy 11, while no abnormality (2 signals) was noted in 23/53 (%) pts. There was no significant difference in the stage, B2M or extent of marrow involvement among patient with or without aberration of ATM gene. Up to 15–20% of the pts with B-cell lymphoproliferative disorders (CLL, mantle cell and other NHL) are reported to have ATM deletion suggesting a possible role of ATM protein in the pathogenesis of at least a subset of these disorders. Even though MM is a B-cell disorder, in our observation the prevalence of ATM deletion in these pts is uncommon and thus unlikely to be a major factor in the pathogenesis of MM.