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Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations

Nature communications, 2017-05, Vol.8 (1), p.15290-11, Article 15290 [Peer Reviewed Journal]

Copyright Nature Publishing Group May 2017 ;Copyright © 2017, The Author(s) 2017 The Author(s) ;ISSN: 2041-1723 ;EISSN: 2041-1723 ;DOI: 10.1038/ncomms15290 ;PMID: 28548104

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Title:
Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations
Author: Chang, Jiang ; Tan, Wenle ; Ling, Zhiqiang ; Xi, Ruibin ; Shao, Mingming ; Chen, Mengjie ; Luo, Yingying ; Zhao, Yanjie ; Liu, Yun ; Huang, Xiancong ; Xia, Yuchao ; Hu, Jinlin ; Parker, Joel S ; Marron, David ; Cui, Qionghua ; Peng, Linna ; Chu, Jiahui ; Li, Hongmin ; Du, Zhongli ; Han, Yaling ; Tan, Wen ; Liu, Zhihua ; Zhan, Qimin ; Li, Yun ; Mao, Weimin ; Wu, Chen ; Lin, Dongxin
Subjects: Adult ; Aged ; Alcohol Drinking - adverse effects ; Asian Continental Ancestry Group - genetics ; Carcinoma, Squamous Cell - epidemiology ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - pathology ; Carcinoma, Squamous Cell - prevention & control ; Cell Cycle - genetics ; China ; DNA Copy Number Variations - drug effects ; DNA Copy Number Variations - genetics ; Esophageal Neoplasms - epidemiology ; Esophageal Neoplasms - genetics ; Esophageal Neoplasms - pathology ; Esophageal Neoplasms - prevention & control ; Esophageal Squamous Cell Carcinoma ; Esophagus - pathology ; Ethanol - toxicity ; Female ; Genome, Human - genetics ; Humans ; Male ; Middle Aged ; Mutation - drug effects ; Phosphatidylinositol 3-Kinases - metabolism ; Polymorphism, Single Nucleotide - drug effects ; Proto-Oncogene Proteins c-akt - metabolism ; Receptors, LDL - genetics ; Signal Transduction - genetics ; Whole Genome Sequencing
Is Part Of: Nature communications, 2017-05, Vol.8 (1), p.15290-11, Article 15290
Description: Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals with ESCC. We identify six mutational signatures (E1-E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion. The most frequently affected genes by structural variation are LRP1B and TTC28. The aberrant cell cycle and PI3K-AKT pathways seem critical in ESCC. These results establish a comprehensive genomic landscape of ESCC and provide potential targets for precision treatment and prevention of the cancer.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 2041-1723
EISSN: 2041-1723
DOI: 10.1038/ncomms15290
PMID: 28548104
Source: MEDLINE
PubMed Central
ProQuest Central
DOAJ Directory of Open Access Journals

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Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations

Copyright Nature Publishing Group May 2017 ;Copyright © 2017, The Author(s) 2017 The Author(s) ;ISSN: 2041-1723 ;EISSN: 2041-1723 ;DOI: 10.1038/ncomms15290 ;PMID: 28548104

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