Detection of ATM germline variants by the p53 mitotic centrosomal localization test in BRCA1/2-negative patients with early-onset breast cancer

Background: variant atm heterozygotes have an increased risk of developing cancer,cardiovascular diseases,and diabetes. costs and time of sequencing and atm variant complexity make large-scale,general population screenings not cost-effective yet. recently,we developed a straightforward,rapid,and inexpensive test based on p53 mitotic centrosomal localization (p53-mcl) in peripheral blood mononuclear cells (pbmcs) that diagnoses mutant atm zygosity and recognizes tumor-associated atm polymorphisms. methods: fresh pbmcs from 496 cancer patients were analyzed by p53-mcl: 90 cases with familial brca1/2-positive and -negative breast and/or ovarian cancer,337 with sporadic cancers (ovarian,lung,colon,and post-menopausal breast cancers),and 69 with breast/thyroid cancer. variants were confirmed by atm sequencing. results: a total of seven individuals with atm variants were identified,5/65 (7.7 %) in breast cancer cases of familial breast and/or ovarian cancer and 2/69 (2.9 %) in breast/thyroid cancer. no variant atm carriers were found among the other cancer cases. excluding a single case in which both brca1 and atm were mutated,no p53-mcl alterations were observed in brca1/2-positive cases. conclusions: these data validate p53-mcl as reliable and specific test for germline atm variants,confirm atm as breast cancer susceptibility gene,and highlight a possible association with breast/thyroid cancers. © 2016 the author(s).