title: Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease and LKS Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease and LKS Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong.
authors.forename: William K K
authors.initials: WK
authors.lastname: Wu
authors.affiliation: Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease and LKS Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong Beijing Genomics Institute at Shenzhen, Shenzhen, China.
authors.forename: Xiangchun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease and LKS Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong Beijing Genomics Institute at Shenzhen, Shenzhen, China.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease and LKS Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Li
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Simon S M
authors.initials: SS
authors.lastname: Ng
authors.affiliation: Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease and LKS Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong Beijing Genomics Institute at Shenzhen, Shenzhen, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease and LKS Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong Beijing Genomics Institute at Shenzhen, Shenzhen, China.
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Beijing Genomics Institute at Shenzhen, Shenzhen, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Beijing Genomics Institute at Shenzhen, Shenzhen, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: Beijing Genomics Institute at Shenzhen, Shenzhen, China.
authors.forename: Qiaoxiu
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease and LKS Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Qiaoyi
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Department of Anatomical & Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Anatomical & Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Joanna H
authors.initials: JH
authors.lastname: Tong
authors.affiliation: Department of Anatomical & Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Ka F
authors.initials: KF
authors.lastname: To
authors.affiliation: Department of Anatomical & Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wong
authors.affiliation: Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease and LKS Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong Department of Gastroenterology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Youyong
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Paul B S
authors.initials: PB
authors.lastname: Lai
authors.affiliation: Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease and LKS Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Francis K L
authors.initials: FK
authors.lastname: Chan
authors.affiliation: Beijing Genomics Institute at Shenzhen, Shenzhen, China.
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.affiliation: Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Hsiang-Fu
authors.initials: HF
authors.lastname: Kung
authors.affiliation: Beijing Genomics Institute at Shenzhen, Shenzhen, China.
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.affiliation: Beijing Genomics Institute at Shenzhen, Shenzhen, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease and LKS Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Joseph J Y
authors.initials: JJ
authors.lastname: Sung
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D011379:Prognosis
keywords: COLONIC NEOPLASMS