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

• DOI: 10.1186/s13046-016-0410-3
• Publication Date: 2016-09-06T05:56:29Z
• Authors: Andrea Prodosmo; Amelia Buffone; Manlio Mattioni; Agnese Barnabei; Agnese Persichetti; Aurora De Leo; Marialuisa Appete...; Arianna Nicolussi; Anna Coppa; Salvatore Sciacch...; Carolina Giordano; Paola Pinnarò; Giuseppe Sanguineti; Lidia Strigari; Gabriele Alessand...; Francesco Facciolo; Maurizio Cosimelli; Gian Luca Grazi; Giacomo Corrado; Enrico Vizza; Giuseppe Giannini; Silvia Soddu
• Keywords: Adult; Aged, 80 and over; BRCA2 Protein; Centrosome; 0303 health sciences; BRCA1 Protein; Research; Mitosis; Breast Neoplasms; Ataxia Telangiectasia Mutated Proteins; Middle Aged; 3. Good health; 03 medical and health sciences; ATM cancer susceptibility gene; BRCA1/2; Early-onset breast cancer; p53-mitotic centrosomal localization (p53-MCL); ATM cancer susceptibility gene; BRCA1/2; early-onset breast cancer; p53-mitotic centrosomal localization (p53-MCL); oncology; Cancer Research; Humans; Female; Genetic Predisposition to Disease; Genetic Testing; Age of Onset; Tumor Suppressor Protein p53; Germ-Line Mutation; Aged

Variant ATM heterozygotes have an increased risk of developing cancer, cardiovascular diseases, and diabetes. Costs time sequencing variant complexity make large-scale, general population screenings not cost-effective yet. Recently, we developed a straightforward, rapid, inexpensive test based on p53 mitotic centrosomal localization (p53-MCL) in peripheral blood mononuclear cells (PBMCs) that diagnoses mutant zygosity recognizes tumor-associated polymorphisms. Fresh PBMCs from 496 cancer patients were analyzed by p53-MCL: 90 cases with familial BRCA1/2-positive -negative breast and/or ovarian 337 sporadic cancers (ovarian, lung, colon, post-menopausal cancers), 69 breast/thyroid cancer. Variants confirmed sequencing. A total seven individuals variants identified, 5/65 (7.7 %) 2/69 (2.9 No carriers found among the other cases. Excluding single case which both BRCA1 mutated, no p53-MCL alterations observed These data validate as reliable specific for germline variants, confirm susceptibility gene, highlight possible association cancers.