IR@PKUHSC  > 北京大学临床肿瘤学院
学科主题临床医学
Clinical Significance of a Point Mutation in DNA Polymerase Beta (POLB) Gene in Gastric Cancer
Tan, Xiaohui1; Wang, Hongyi2; Luo, Guangbin3; Ren, Shuyang1; Li, Wenmei1; Cui, Jiantao1; Gill, Harindarpal S.4; Fu, Sidney W.4; Lu, Youyong1
关键词DNA polymerase beta (POLB) gastric cancer DNA Repair point mutation chemotherapy
刊名INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
2015
DOI10.7150/ijbs.10692
11期:2页:144-155
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Biology
研究领域[WOS]Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
关键词[WOS]BASE EXCISION-REPAIR ; NEGATIVE BREAST-CANCER ; COLORECTAL-CANCER ; MURINE MELANOMA ; CELL-LINES ; DEFICIENCY ; OVEREXPRESSION ; CARCINOMAS ; THERAPY ; VARIANT
英文摘要

Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal adjacent tissues were collected at the time of surgery. DNA, RNA and protein samples were isolated from GC specimens and cell lines. Mutations were detected by PCR-RFLP/DHPLC and sequencing analysis. POLB gene expression was examined by RT-PCR, tissue microarray, Western blotting and immunofluorescence assays. The function of the mutation was evaluated by chemosensitivity, MTT, Transwell matrigel invasion and host cell reactivation assays. The T889C mutation was detected in 18 (10.17%) of 177 GC patients. And the T889C mutation was associated with POLB overexpression, lymph nodes metastases and poor tumor differentiation. In addition, patients with-the mutation had significantly shorter survival time than those without-, following postoperative chemotherapy. Furthermore, cell lines with T889C mutation in POLB gene were more resistant to the treatment of 5-fluorouracil, cisplatin and epirubicin than those with wild type POLB. Forced expression of POLB gene with T889C mutation resulted in enhanced cell proliferation, invasion and resistance to anticancer drugs, along with increased DNA repair capability. These results suggest that POLB gene with T889C mutation in surgically resected primary gastric tissues may be clinically useful for predicting responsiveness to chemotherapy in patients with GC. The POLB gene alteration may serve as a prognostic biomarker for GC.

语种英语
WOS记录号WOS:000350408200003
项目编号2004CB518708 ; 39625016 ; 2012-AA02A203 ; K01DK082646
资助机构National Key Basic Research Program Project of China ; National Natural Science Foundation of China (NSFC) ; National Bio-Tech 863 Program ; NIDDK/NIH ; Elaine H. Snyder Cancer Research Award
引用统计
被引频次:9[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59517
专题北京大学临床肿瘤学院
作者单位1.Minist Educ, Key Lab Carcinogenesis & Translat Res, Mol Oncol Lab, Beijing, Peoples R China
2.Peking Univ, Beijing Canc Hosp & Inst, Sch Oncol, Dept Sugary, Beijing 100142, Peoples R China
3.Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA
4.George Washington Univ, Sch Med & Hlth Sci, Dept Med, Washington, DC 20037 USA
推荐引用方式
GB/T 7714
Tan, Xiaohui,Wang, Hongyi,Luo, Guangbin,et al. Clinical Significance of a Point Mutation in DNA Polymerase Beta (POLB) Gene in Gastric Cancer[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2015,11(2):144-155.
APA Tan, Xiaohui.,Wang, Hongyi.,Luo, Guangbin.,Ren, Shuyang.,Li, Wenmei.,...&Lu, Youyong.(2015).Clinical Significance of a Point Mutation in DNA Polymerase Beta (POLB) Gene in Gastric Cancer.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,11(2),144-155.
MLA Tan, Xiaohui,et al."Clinical Significance of a Point Mutation in DNA Polymerase Beta (POLB) Gene in Gastric Cancer".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 11.2(2015):144-155.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Tan, Xiaohui]的文章
[Wang, Hongyi]的文章
[Luo, Guangbin]的文章
百度学术
百度学术中相似的文章
[Tan, Xiaohui]的文章
[Wang, Hongyi]的文章
[Luo, Guangbin]的文章
必应学术
必应学术中相似的文章
[Tan, Xiaohui]的文章
[Wang, Hongyi]的文章
[Luo, Guangbin]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。