Frequency and spectrum of ATM mutations in Bulgarian breast cancer patients

Germline mutations in ATM gene lead to a rare hereditary syndrome, Ataxia-Telangiectasia (A-T), characterized with oculocutaneous telangiectases, an increased incidence of cancer, hypersensitivity to ionizing radiation and chromosomal instability. Women heterozygous for ATM show a relative risk to develop cancer, with breast cancer being most prevalent. Hence, it is critical to investigate whether ATM mutations result in breast cancer susceptibility. PCR-SSCP-sequencing analysis was performed in 17 specific exons of ATM gene to estimate the type and frequency of mutations in a group of 145 Bulgarian breast cancer patients. A total of 11 patients with ATM mutations were identified. Two mis-sense variants - pSer707Pro (T>C) and pAsp1853Asn (G>A), and four identical intronic variants IVS38-8 T>C were found. Our data showed that ATM mutational frequency is 7.59%. Comparison with clinical characteristics showed that in the group with ATM mutation the carcinogenic process has an early age expression, but is less aggressive, confirmed by the grade of malignancy G (p=0.032). Identifying carriers of mutations in the ATM gene will contribute to assessment of its role in breast cancer pathogenesis. (authors)