Cargando…

Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer

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 sign...

Descripción completa

Detalles Bibliográficos
Autores principales: Yu, Jun, Wu, William K K, Li, Xiangchun, He, Jun, Li, Xiao-Xing, Ng, Simon S M, Yu, Chang, Gao, Zhibo, Yang, Jie, Li, Miao, Wang, Qiaoxiu, Liang, Qiaoyi, Pan, Yi, Tong, Joanna H, To, Ka F, Wong, Nathalie, Zhang, Ning, Chen, Jie, Lu, Youyong, Lai, Paul B S, Chan, Francis K L, Li, Yingrui, Kung, Hsiang-Fu, Yang, Huanming, Wang, Jun, Sung, Joseph J Y
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392212/
https://www.ncbi.nlm.nih.gov/pubmed/24951259
http://dx.doi.org/10.1136/gutjnl-2013-306620
_version_ 1782365945864388608
author Yu, Jun
Wu, William K K
Li, Xiangchun
He, Jun
Li, Xiao-Xing
Ng, Simon S M
Yu, Chang
Gao, Zhibo
Yang, Jie
Li, Miao
Wang, Qiaoxiu
Liang, Qiaoyi
Pan, Yi
Tong, Joanna H
To, Ka F
Wong, Nathalie
Zhang, Ning
Chen, Jie
Lu, Youyong
Lai, Paul B S
Chan, Francis K L
Li, Yingrui
Kung, Hsiang-Fu
Yang, Huanming
Wang, Jun
Sung, Joseph J Y
author_facet Yu, Jun
Wu, William K K
Li, Xiangchun
He, Jun
Li, Xiao-Xing
Ng, Simon S M
Yu, Chang
Gao, Zhibo
Yang, Jie
Li, Miao
Wang, Qiaoxiu
Liang, Qiaoyi
Pan, Yi
Tong, Joanna H
To, Ka F
Wong, Nathalie
Zhang, Ning
Chen, Jie
Lu, Youyong
Lai, Paul B S
Chan, Francis K L
Li, Yingrui
Kung, Hsiang-Fu
Yang, Huanming
Wang, Jun
Sung, Joseph J Y
author_sort Yu, Jun
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4392212
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BMJ Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-43922122015-04-13 Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer Yu, Jun Wu, William K K Li, Xiangchun He, Jun Li, Xiao-Xing Ng, Simon S M Yu, Chang Gao, Zhibo Yang, Jie Li, Miao Wang, Qiaoxiu Liang, Qiaoyi Pan, Yi Tong, Joanna H To, Ka F Wong, Nathalie Zhang, Ning Chen, Jie Lu, Youyong Lai, Paul B S Chan, Francis K L Li, Yingrui Kung, Hsiang-Fu Yang, Huanming Wang, Jun Sung, Joseph J Y Gut Colon 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. BMJ Publishing Group 2015-04 2014-06-20 /pmc/articles/PMC4392212/ /pubmed/24951259 http://dx.doi.org/10.1136/gutjnl-2013-306620 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Colon
Yu, Jun
Wu, William K K
Li, Xiangchun
He, Jun
Li, Xiao-Xing
Ng, Simon S M
Yu, Chang
Gao, Zhibo
Yang, Jie
Li, Miao
Wang, Qiaoxiu
Liang, Qiaoyi
Pan, Yi
Tong, Joanna H
To, Ka F
Wong, Nathalie
Zhang, Ning
Chen, Jie
Lu, Youyong
Lai, Paul B S
Chan, Francis K L
Li, Yingrui
Kung, Hsiang-Fu
Yang, Huanming
Wang, Jun
Sung, Joseph J Y
Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer
title Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer
title_full Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer
title_fullStr Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer
title_full_unstemmed Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer
title_short Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer
title_sort novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer
topic Colon
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392212/
https://www.ncbi.nlm.nih.gov/pubmed/24951259
http://dx.doi.org/10.1136/gutjnl-2013-306620
work_keys_str_mv AT yujun novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT wuwilliamkk novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT lixiangchun novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT hejun novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT lixiaoxing novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT ngsimonsm novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT yuchang novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT gaozhibo novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT yangjie novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT limiao novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT wangqiaoxiu novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT liangqiaoyi novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT panyi novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT tongjoannah novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT tokaf novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT wongnathalie novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT zhangning novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT chenjie novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT luyouyong novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT laipaulbs novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT chanfranciskl novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT liyingrui novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT kunghsiangfu novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT yanghuanming novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT wangjun novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer
AT sungjosephjy novelrecurrentlymutatedgenesandaprognosticmutationsignatureincolorectalcancer