Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis
| Autor: | Shao Dan Zhang, Shao Yi Huang, Ye Zhu Hu, Fang Fang Li, Benjamin Lehrman, Dongxin Lin, Hai De Qin, Xiao Song Ge, Xi Zhao Li, Qiuyin Cai, Yin Yao Shugart, Alan F. Scott, Yuan Bin Chen, Jirong Long, Wen Qiong Xue, Wei Hua Jia, De Qing Liu, L. J. Zhang, Yi Xin Zeng, Xiao Yu Liao |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Esophageal Neoplasms Carcinogenesis Somatic cell Fas-Associated Death Domain Protein Cell Cycle Proteins medicine.disease_cause Mice 0302 clinical medicine Genetics(clinical) Exome Genetics (clinical) Aged 80 and over Genetics Mice Inbred BALB C Mutation Middle Aged Prognosis 3. Good health Gene Expression Regulation Neoplastic 030220 oncology & carcinogenesis Carcinoma Squamous Cell Female Esophageal Squamous Cell Carcinoma Adult DNA Copy Number Variations Nerve Tissue Proteins Biology Article 03 medical and health sciences Cell Line Tumor microRNA medicine Carcinoma Animals Humans Selection Genetic Gene Genetic Association Studies Aged Cell Proliferation Gene Expression Profiling Membrane Proteins medicine.disease Xenograft Model Antitumor Assays Gene expression profiling MicroRNAs 030104 developmental biology Trans-Activators Carrier Proteins |
| Zdroj: | The American Journal of Human Genetics. 98:709-727 |
| ISSN: | 0002-9297 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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