The Novel Pathogenic Mutation c.849dupT in BRCA2 Contributes to the Nonsense-Mediated mRNA Decay of BRCA2 in Familial Breast Cancer / 한국유방암학회지

In this study, we used next-generation sequencing methods to screen 300 individuals for BRCA1 and BRCA2. A novel mutation (c.849dupT) in BRCA2 was identified in a female patient and her unaffected brothers. This mutation leads to the truncation of BRCA2 functional domains. Moreover, BRCA2 mRNA expression levels in mutation carriers are significantly reduced compared to noncarriers. Immunofluorescence and western blot assays showed that this mutation resulted in reduced BRCA2 protein expression. Thus, we identified a novel mutation that damaged the function and expression of BRCA2 in a family with breast cancer history. The pedigree analysis suggested that this mutation is strongly associated with familial breast cancer. Genetic counsellors suggest that mutation carriers in this family undergo routine screening for breast cancer, as well as other malignancies, such as prostate and ovarian cancer. The effects of this BRCA2 mutation on drug resistance should be taken into consideration during treatment.

The expression changes of cancer-related pathways genes screened by RT-PCR Array in bladder cancer / 中国癌症杂志

Background and purpose:Bladder cancer is the most common urological tumor, and its pathogen-esis is still not fully understood. The study was aimed to observe the expressions of key genes in many tumor-associated signaling pathways in normal bladder tissue and bladder carcinoma, and to provide further evidence for the subsequent study of bladder cancer recurrence and metastasis.Methods:Twenty-seven cases of bladder cancer specimens were col-lected, and normal bladder tissues and bladder cancer tissues were distinguished by frozen section. Then, the expressions of 84 genes of cancer-related signaling pathways in bladder cancer tissues and normal bladder tissues were screened by Cancer Pathway Finder PCR Array produced by QIAGEN company.Results:Compared with the normal bladder tissues, the bladder carcinoma tissues had 8 up-regulated genes and 19 down-regulated genes. In this study, the impact of epithe-lial-mesenchymal transition (EMT) signaling pathway was selected as a research direction in which theGSC,KRT14,DSP were up-regulated,SNAI2,SNAI3 were down-regulated. ThereforeGSC,KRT14,DSP,SNAI2 andSNAI3 were chosen as target genes, and verified by qRT-PCR in many examples. The result showed that the expressions ofGSC gene in bladder cancer tissues were up-regulated, but with no statistical significance;KRT14,DSP expressions in bladder cancer were higher than those in normal bladder tissues (P<0.05);SNAI2,SNAI3 expressions in bladder cancer were lower than those in normal bladder tissues (P<0.05), andSNAI3 showed the most obvious expression differences.Conclusion:KRT14,DSP andSNAI3 may play an important role in bladder cancer’s occurrence, development and metastasis.