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学科主题: 临床医学
题名:
Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer
作者: Yu, Jun1,2; Wu, William K. K.1,2; Li, Xiangchun1,2,3; He, Jun1,2,3; Li, Xiao-Xing1,2; Ng, Simon S. M.4; Yu, Chang1,2,3; Gao, Zhibo1,2,3; Yang, Jie3; Li, Miao3; Wang, Qiaoxiu3; Liang, Qiaoyi1,2; Pan, Yi5; Tong, Joanna H.5; To, Ka F.5; Wong, Nathalie5; Zhang, Ning1,2,6; Chen, Jie6; Lu, Youyong7; Lai, Paul B. S.4; Chan, Francis K. L.1,2; Li, Yingrui3; Kung, Hsiang-Fu8; Yang, Huanming3; Wang, Jun3; Sung, Joseph J. Y.1,2
刊名: GUT
发表日期: 2015-04-01
DOI: 10.1136/gutjnl-2013-306620
卷: 64, 期:4, 页:636-645
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Gastroenterology & Hepatology
研究领域[WOS]: Gastroenterology & Hepatology
关键词[WOS]: COMPREHENSIVE MOLECULAR CHARACTERIZATION ; COLON-CANCER ; MICROSATELLITE INSTABILITY ; SOMATIC MUTATION ; SEQUENCING DATA ; BETA-CATENIN ; ACTIVATION ; EXOME ; IDENTIFICATION ; SURVIVAL
英文摘要:

Background Characterisation of colorectal cancer (CRC) genomes by next-generation sequencing has led to the discovery of novel recurrently mutated genes. Nevertheless, genomic data has not yet been used for CRC prognostication.

Objective To identify recurrent somatic mutations with prognostic significance in patients with CRC.

Method Exome sequencing was performed to identify somatic mutations in tumour tissues of 22 patients with CRC, followed by validation of 187 recurrent and pathway-related genes using targeted capture sequencing in additional 160 cases.

Results Seven significantly mutated genes, including four reported (APC, TP53, KRAS and SMAD4) and three novel recurrently mutated genes (CDH10, FAT4 and DOCK2), exhibited high mutation prevalence (6-14% for novel cancer genes) and higher-than-expected number of non-silent mutations in our CRC cohort. For prognostication, a five-gene-signature (CDH10, COL6A3, SMAD4, TMEM132D, VCAN) was devised, in which mutation(s) in one or more of these genes was significantly associated with better overall survival independent of tumor-node-metastasis (TNM) staging. The median survival time was 80.4 months in the mutant group versus 42.4 months in the wild type group (p= 0.0051). The prognostic significance of this signature was successfully verified using the data set from the Cancer Genome Atlas study.

Conclusions The application of next-generation sequencing has led to the identification of three novel significantly mutated genes in CRC and a mutation signature that predicts survival outcomes for stratifying patients with CRC independent of TNM staging.

语种: 英语
所属项目编号: JCYJ JCYJ20120619152326450 ; 2012AA02A506 ; 2013CB531401 ; T12-403-11
项目资助者: Cancer Genome Project of the Chinese University of Hong Kong ; Shenzhen Municipal Science and Technology RD ; China 863 program fund ; Theme-based Research Scheme of Hong Kong RGC ; Shenzhen Virtual University Park Support Scheme
WOS记录号: WOS:000350800100019
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54468
Appears in Collections:北京大学临床肿瘤学院_分子肿瘤学研究室_期刊论文

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作者单位: 1.Beijing Genom Inst Shenzhen, Shenzhen 518000, Peoples R China
2.Chinese Univ Hong Kong, Dept Med & Therapeut, State Key Lab Digest Dis, Inst Digest Dis, Shatin, Hong Kong, Peoples R China
3.Chinese Univ Hong Kong, LKS Inst Hlth Sci, CUHK Shenzhen Res Inst, Shatin, Hong Kong, Peoples R China
4.Chinese Univ Hong Kong, Dept Surg, Shatin, Hong Kong, Peoples R China
5.Chinese Univ Hong Kong, Dept Anat & Cellular Pathol, Shatin, Hong Kong, Peoples R China
6.Sun Yat Sen Univ, Affiliated Hosp 1, Dept Gastroenterol, Guangzhou 510275, Guangdong, Peoples R China
7.Peking Univ, Canc Hosp & Inst, Lab Mol Oncol, Beijing 100871, Peoples R China
8.Chinese Univ Hong Kong, Stanley Ho Ctr Emerging Infect Dis, Shatin, Hong Kong, Peoples R China

Recommended Citation:
Yu, Jun,Wu, William K. K.,Li, Xiangchun,et al. Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer[J]. GUT,2015,64(4):636-645.
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