title: Genomic analyses reveal FAM84B and the NOTCH pathway are associated with the progression of esophageal squamous cell carcinoma.
abstract: BACKGROUND
  Esophageal squamous cell carcinoma (ESCC) is the sixth most lethal cancer worldwide and the fourth most lethal cancer in China. Genomic characterization of tumors, particularly those of different stages, is likely to reveal additional oncogenic mechanisms. Although copy number alterations and somatic point mutations associated with the development of ESCC have been identified by array-based technologies and genome-wide studies, the genomic characterization of ESCCs from different stages of the disease has not been explored. Here, we have performed either whole-genome sequencing or whole-exome sequencing on 51 stage I and 53 stage III ESCC patients to characterize the genomic alterations that occur during the various clinical stages of ESCC, and further validated these changes in 36 atypical hyperplasia samples.
  
  
  RESULTS
  Recurrent somatic amplifications at 8q were found to be enriched in stage I tumors and the deletions of 4p-q and 5q were particularly identified in stage III tumors. In particular, the FAM84B gene was amplified and overexpressed in preclinical and ESCC tumors. Knockdown of FAM84B in ESCC cell lines significantly reduced in vitro cell growth, migration and invasion. Although the cancer-associated genes TP53, PIK3CA, CDKN2A and their pathways showed no significant difference between stage I and stage III tumors, we identified and validated a prevalence of mutations in NOTCH1 and in the NOTCH pathway that indicate that they are involved in the preclinical and early stages of ESCC.
  
  
  CONCLUSIONS
  Our results suggest that FAM84B and the NOTCH pathway are involved in the progression of ESCC and may be potential diagnostic targets for ESCC susceptibility.
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Department of Pathology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Heyang
authors.initials: H
authors.lastname: Cui
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Department of Oncology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Bin
authors.initials: B
authors.lastname: Song
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Department of Tumor Surgery, Shanxi Cancer Hospital, Taiyuan, Shanxi 030001 China.
authors.forename: Yaoping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Department of General Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Pengzhou
authors.initials: P
authors.lastname: Kong
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Ruyi
authors.initials: R
authors.lastname: Shi
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Yanghui
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Department of Tumor Surgery, Shanxi Cancer Hospital, Taiyuan, Shanxi 030001 China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Zhenxiang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Department of General Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Hu
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Chanting
authors.initials: C
authors.lastname: He
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi 030001 China.
authors.forename: Jinfen
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi 030001 China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi 030001 China.
authors.forename: Enwei
authors.initials: E
authors.lastname: Xu
authors.affiliation: Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi 030001 China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Tumor Surgery, Shanxi Cancer Hospital, Taiyuan, Shanxi 030001 China.
authors.forename: Shiping
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Tumor Surgery, Shanxi Cancer Hospital, Taiyuan, Shanxi 030001 China.
authors.forename: Yunqing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Urology Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Endoscopy, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030001 China.
authors.forename: Xing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pathology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of General Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Guo
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620 China.
authors.forename: Chuangui
authors.initials: C
authors.lastname: Wang
authors.affiliation: Cancer Institute and Cancer Hospital, State Key Laboratory of Molecular Oncology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China.
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
authors.affiliation: Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001 China ; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001 China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Cui
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002872:Chromosome Deletion; D056915:DNA Copy Number Variations; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000235:genetics; D034622:RNA Interference; D051880:Receptors, Notch / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: C585865:LRATD2 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D051880:Receptors, Notch
keywords: ESCC; FAM84B; NOTCH signaling; Next-generation sequencing