To investigate germline mutation of breast cancer susceptibility genes BRCA1/2, TP53 and PTEN in Chinese breast cancer patients.

All of128 female breast cancer patients in Peking University People′s Hospital from January 2016 to August 2018 were selected as objects. Among them, 44 cases were sporadic breast cancer and 84 werebreast cancer patients with genetic high risks. Germline mutations of BRCA1, BRCA2, TP53 and PTENwere detected by NGS. χ² test was used to analyze the difference of pathogenic mutation rates between sporadic breast cancer group and breast cancer with high genetic risks.Groups were divided according to the clinical features of the patients (family history, triple-negative breast cancer, age and bilateral breast cancer) .Among them, there were 42 cases with family history of breast cancer, 34 cases of triple-negative breast cancer, 33 cases of early-onset breast cancer and 7 cases of bilateral breast cancer. Fisher′s exact probability test compared the relationship between pathogenic mutations of BRCA1/2 gene and clinical characteristics of breast cancer patients with hereditary risk factors.

In 128 cases of breast cancer, 30 germline mutations of BRCA1/2 were detected, including 13 pathogenic mutations and 3 newly discovered mutations (BRCA1: c.4760C>G, BRCA2: c.4413_4414del and BRCA2: c.6482_6485del) . The new mutations may be unique mutations of Chinese population. There were 3 cases of TP53 mutations, including 1 pathogenic mutation. All of the 3 mutations were found in early-onset breast cancer. Germline mutation of T53 has important detection significance for early-onset hereditary breast cancer. There were 5 cases of PTEN mutations, including 3 pathogenic mutations. Among 84 breast cancer patients with genetic high risks, the carry mutation rate was 40.5% (34/84) and the pathogenic mutation rate was 15.4 (13/84) . Among 44 sporadic cases, the carry mutation rate was 9% (4/44) . The pathogenic mutation rate was 6.8% (3/44) . Breast cancer susceptibility genes were carried at a higher rate in breast cancer patients with genetic high risks (P<0.001) . BRCA1/2 mutations did not show statistical differences among groups of breast cancer patients with hereditary high risk factors.

Germline mutation detection of breast cancer susceptibility genes by next-generation sequencing is of great significance in breast cancer risk prediction and prognosis evaluation.

Breast neoplasms; High-throughput nucleotide sequencing; Genes, BRCA1; PTEN phosphohydrolase; Genes, p53; Genetic predisposition to disease