@article{86889b2cd11d4629a24642ed0d12c368,
title = "Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis",
abstract = "The genetic mechanisms underlying the poor prognosis of esophageal squamous cell carcinoma (ESCC) are not well understood. Here, we report somatic mutations found in ESCC from sequencing 10 whole-genome and 57 whole-exome matched tumor-normal sample pairs. Among the identified genes, we characterized mutations in VANGL1 and showed that they accelerated cell growth in vitro. We also found that five other genes, including three coding genes (SHANK2, MYBL2, FADD) and two non-coding genes (miR-4707-5p, PCAT1), were involved in somatic copy-number alterations (SCNAs) or structural variants (SVs). A survival analysis based on the expression profiles of 321 individuals with ESCC indicated that these genes were significantly associated with poorer survival. Subsequently, we performed functional studies, which showed that miR-4707-5p and MYBL2 promoted proliferation and metastasis. Together, our results shed light on somatic mutations and genomic events that contribute to ESCC tumorigenesis and prognosis and might suggest therapeutic targets.",
author = "Qin, {Hai De} and Liao, {Xiao Yu} and Chen, {Yuan Bin} and Huang, {Shao Yi} and Xue, {Wen Qiong} and Li, {Fang Fang} and Ge, {Xiao Song} and Liu, {De Qing} and Qiuyin Cai and Jirong Long and Li, {Xi Zhao} and Hu, {Ye Zhu} and Zhang, {Shao Dan} and Zhang, {Lan Jun} and Benjamin Lehrman and Scott, {Alan F.} and Dongxin Lin and Zeng, {Yi Xin} and Shugart, {Yin Yao} and Jia, {Wei Hua}",
note = "Funding Information: We{\textquoteright}d like to thank Profs. Xiao-ou Shu and Wei Zheng of the Vanderbilt-Ingram Cancer Center for their kind advice in the course of sample preparation, exon capture, and deep sequencing. We thank Prof. Song Gao for his kind help in protein structure prediction. We also thank Bank of Tumor Resources, Cancer Center Sun Yat-sen University for providing the ESCC samples in this study. This work was supported by the grants from the National Science Fund for Distinguished Young Scholars of China (grant no. 81325018), the Key Project for International Cooperation and Exchange of the National Natural Science Foundation of China (grant no. 81220108022), the National Basic Research Program of China (973 program no. 2011CB504303). The authors gratefully acknowledge the support of the Intramural Research Program, National Institute of Mental Health (NIMH), NIH (IRP-NIMH-NIH, grant no. MH002930-05). The views expressed in this presentation do not necessarily represent the views of the the NIMH, the NIH, the US Department of Health and Human Services, or the United States Government. Publisher Copyright: {\textcopyright} 2016 The American Society of Human Genetics. All rights reserved.",
year = "2016",
month = apr,
day = "7",
doi = "10.1016/j.ajhg.2016.02.021",
language = "English (US)",
volume = "98",
pages = "709--727",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "4",
}