| Literature DB >> 27058444 |
Hai-De Qin1, Xiao-Yu Liao2, Yuan-Bin Chen2, Shao-Yi Huang2, Wen-Qiong Xue2, Fang-Fang Li2, Xiao-Song Ge3, De-Qing Liu2, Qiuyin Cai4, Jirong Long4, Xi-Zhao Li2, Ye-Zhu Hu2, Shao-Dan Zhang2, Lan-Jun Zhang2, Benjamin Lehrman5, Alan F Scott6, Dongxin Lin7, Yi-Xin Zeng2, Yin Yao Shugart8, Wei-Hua Jia9.
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.Entities:
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Year: 2016 PMID： 27058444 PMCID： PMC4833434 DOI： 10.1016/j.ajhg.2016.02.021
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025