Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer.

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.

Clinical implications of stem cell gene Oct-4 expression in breast cancer.

PURPOSE: To explore the expression of stem cell genes in breast cancer and the relationship between stem cell gene expression and clinical and pathological characteristics and prognosis of breast cancer. BACKGROUND: By now, stem cell differentiation-related genes and the relationship between the genes and clinic-pathological characteristics and prognosis of breast cancer are still unclear. MATERIALS AND METHODS: CD44+/CD24- tumor cells were selected by Flow cytometry. The differential expression of genes between CD44+/CD24- tumor cells and non-CD44+/CD24- tumor cells were detected by RT(2) Profiler™ PCR Array. The expression of stem cell gene Octamer-4 (Oct-4) was analyzed by immunohistochemistry staining and the relationship between Oct-4 and clinicopathological parameters of breast cancer was determined. RESULTS: Seven different genes including stem cell differentiation-related factors (CD44, Oct-4, and nestin), cell cycle regulators (APC and CDC2), and growth factors (HGF and TGF) were detected as significantly differently expressed between CD44+/CD24- tumor cells and non-CD44+/CD24- tumor cells. Oct-4 protein expressed significantly higher in cancerous tissues than adjacent-tumor tissues (P = 0.001). Moreover, we observed that the expression of Oct-4 protein was related to histological type, lymph node status and molecular type of breast cancer (P = 0.001, 0.006, and 0.001, respectively). After survival analysis, the cases with highly expressed Oct-4 protein attained a significantly poorer postoperative disease-specific survival than those with none/low expressed Oct-4 protein (P = 0.001). In the Cox regression test, tumor size, histological type, disease stage, lymph node metastasis, Her-2 and Oct-4 were detected as the independent prognostic factors (P = 0.031, 0.012, 0.001, 0.002, 0.030, and 0.003, respectively). CONCLUSIONS: Oct-4 was highly expressed in CD44+/CD24- tumor cells, and may be a potential biomarker for the initiation, progression, and differentiation of breast cancer.