Identification of genomic alterations in oesophageal squamous cell cancer

Song, Yongmei, Li, Lin, Ou, Yunwei, Gao, Zhibo, Li, Enmin, Li, Xiangchun, Zhang, Weimin, Wang, Jiaqian, Xu, Liyan, Zhou, Yong, Ma, Xiaojuan, Liu, Lingyan, Zhao, Zitong, Huang, Xuanlin, Fan, Jing, Dong, Lijia, Chen, Gang, Ma, Liying, Yang, Jie, Chen, Longyun, He, Minghui, Li, Miao, Zhuang, Xuehan, Huang, Kai, Qiu, Kunlong, Yin, Guangliang, Guo, Guangwu, Feng, Qiang, Chen, Peishan, Wu, Zhiyong, Wu, Jianyi, Ma, Ling, Zhao, Jinyang, Luo, Longhai, Fu, Ming, Xu, Bainan, Chen, Bo, Li, Yingrui, Tong, Tong, Wang, Mingrong, Liu, Zhihua, Lin, Dongxin, Zhang, Xiuqing, Yang, Huanming, Wang, Jun and Zhan, Qimin (2014) Identification of genomic alterations in oesophageal squamous cell cancer. Nature, 509 7498: 91-95. doi:10.1038/nature13176

Author Song, Yongmei
Li, Lin
Ou, Yunwei
Gao, Zhibo
Li, Enmin
Li, Xiangchun
Zhang, Weimin
Wang, Jiaqian
Xu, Liyan
Zhou, Yong
Ma, Xiaojuan
Liu, Lingyan
Zhao, Zitong
Huang, Xuanlin
Fan, Jing
Dong, Lijia
Chen, Gang
Ma, Liying
Yang, Jie
Chen, Longyun
He, Minghui
Li, Miao
Zhuang, Xuehan
Huang, Kai
Qiu, Kunlong
Yin, Guangliang
Guo, Guangwu
Feng, Qiang
Chen, Peishan
Wu, Zhiyong
Wu, Jianyi
Ma, Ling
Zhao, Jinyang
Luo, Longhai
Fu, Ming
Xu, Bainan
Chen, Bo
Li, Yingrui
Tong, Tong
Wang, Mingrong
Liu, Zhihua
Lin, Dongxin
Zhang, Xiuqing
Yang, Huanming
Wang, Jun
Zhan, Qimin
Title Identification of genomic alterations in oesophageal squamous cell cancer
Journal name Nature   Check publisher's open access policy
ISSN 1476-4687
Publication date 2014-03-16
Year available 2014
Sub-type Letter to editor, brief commentary or brief communication
DOI 10.1038/nature13176
Open Access Status Not Open Access
Volume 509
Issue 7498
Start page 91
End page 95
Total pages 5
Publisher Nature Publishing Group
Language eng
Formatted abstract
Oesophageal cancer is one of the most aggressive cancers and is the sixth leading cause of cancer death worldwide. Approximately 70% of global oesophageal cancer cases occur in China, with oesophageal squamous cell carcinoma (ESCC) being the histopathological form in the vast majority of cases (>90%). Currently, there are limited clinical approaches for the early diagnosis and treatment of ESCC, resulting in a 10% five-year survival rate for patients. However, the full repertoire of genomic events leading to the pathogenesis of ESCC remains unclear. Here we describe a comprehensive genomic analysis of 158 ESCC cases, as part of the International Cancer Genome Consortium research project. We conducted whole-genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases, of which 53 cases, plus an additional 70 ESCC cases not used in the whole-genome and whole-exome sequencing, were subjected to array comparative genomic hybridization analysis. We identified eight significantly mutated genes, of which six are well known tumour-associated genes (TP53, RB1, CDKN2A, PIK3CA, NOTCH1, NFE2L2), and two have not previously been described in ESCC (ADAM29 and FAM135B). Notably, FAM135B is identified as a novel cancer-implicated gene as assayed for its ability to promote malignancy of ESCC cells. Additionally, MIR548K, a microRNA encoded in the amplified 11q13.3-13.4 region, is characterized as a novel oncogene, and functional assays demonstrate that MIR548K enhances malignant phenotypes of ESCC cells. Moreover, we have found that several important histone regulator genes (MLL2 (also called KMT2D), ASH1L, MLL3 (KMT2C), SETD1B, CREBBP and EP300) are frequently altered in ESCC. Pathway assessment reveals that somatic aberrations are mainly involved in the Wnt, cell cycle and Notch pathways. Genomic analyses suggest that ESCC and head and neck squamous cell carcinoma share some common pathogenic mechanisms, and ESCC development is associated with alcohol drinking. This study has explored novel biological markers and tumorigenic pathways that would greatly improve therapeutic strategies for ESCC.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Letter to editor, brief commentary or brief communication
Collection: Institute for Molecular Bioscience - Publications
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