乳腺癌特异性拷贝数变异致DNA修复失衡

Imbalance of DNA Repair Caused by Breast Cancer Specific Copy Number Variation

该研究通过整合4个功能诠释数据库(KEGG、GO、WIKI和PC)共发现56条DNA修复相关通路,确定了725个功能基因;并在筛查CCLE肿瘤细胞系和TCGA乳腺癌基因组数据的基础上,发现了89个乳腺癌特异性的拷贝数变异基因,其中包含了4个DNA修复相关的基因[BRCA1(breast cancer 1,early onset)、ERBB2(erb-b2 receptor tyrosine kinase 2)、G6PC(glucose-6-phosphatase,catalytic subunit)和PSME3(proteasome(prosome,macropain)activator subunit 3(PA28 gamma;Ki))]。进一步生物信息分析表明,乳腺癌基因组中17q21.31区域的拷贝数变异可通过改变BRCA1和PSME3基因的表达,从而影响DNA修复功能(如双链的断裂修复和DNA损伤相关检测点)。

We integrated 56 pathways related to DNA repair from databases （KEGG, GO, WIKI and PC）, and identified 725 DNA repair genes. Based on the genomic data from CCLE and TCGA, we detected four candidates related to DNA repair （BRCAI, ERBB2, G6PC and PSME3） from 89 genes mapped to the copy number variation （CNV） restricted in breast cancer. Further interpretation revealed that the CNV of 17@1.31 could affect the DNA repair （such as ＂double strand breaks repair＂ and ＂DNA damage related detection point＂） by changing the expression of BRCA1 and PSME3 in breast cancer.