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.
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; Unit on Statistical Genomics, Division of Intramural Research Programs, National Institute of Mental Health, NIH, Bethesda, MD 20892, USA.
authors.forename: Hai-De
authors.initials: HD
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Yuan-Bin
authors.initials: YB
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Shao-Yi
authors.initials: SY
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Wen-Qiong
authors.initials: WQ
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; The Affiliated Hospital of Jiangnan University, Wuxi 214062, China.
authors.forename: Xiao-Song
authors.initials: XS
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: De-Qing
authors.initials: DQ
authors.lastname: Liu
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center and Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37240, USA.
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center and Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37240, USA.
authors.forename: Jirong
authors.initials: J
authors.lastname: Long
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Xi-Zhao
authors.initials: XZ
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Ye-Zhu
authors.initials: YZ
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Shao-Dan
authors.initials: SD
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Lan-Jun
authors.initials: LJ
authors.lastname: Zhang
authors.affiliation: Unit on Statistical Genomics, Division of Intramural Research Programs, National Institute of Mental Health, NIH, Bethesda, MD 20892, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lehrman
authors.affiliation: McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Scott
authors.affiliation: State Key Laboratory of Molecular Oncology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.affiliation: Unit on Statistical Genomics, Division of Intramural Research Programs, National Institute of Mental Health, NIH, Bethesda, MD 20892, USA. Electronic address: kay1yao@mail.nih.gov.
authors.forename: Yin Yao
authors.initials: YY
authors.lastname: Shugart
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China. Electronic address: jiawh@sysucc.org.cn.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D056915:DNA Copy Number Variations; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D059472:Exome; D053200:Fas-Associated Death Domain Protein / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D011379:Prognosis; D012641:Selection, Genetic; D015534:Trans-Activators / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; C064352:MYBL2 protein, human; D008565:Membrane Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; C122162:SHANK2 protein, human; D015534:Trans-Activators; C488287:VANGL1 protein, human