title: Genetic landscape of esophageal squamous cell carcinoma.
abstract: Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1, FAT2, FAT3 or FAT4 (27%) or AJUBA (JUB; 7%) and NOTCH1, NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications.
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yi-Bo
authors.initials: YB
authors.lastname: Gao
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Zhao-Li
authors.initials: ZL
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jia-Gen
authors.initials: JG
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xue-Da
authors.initials: XD
authors.lastname: Hu
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xue-Jiao
authors.initials: XJ
authors.lastname: Shi
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Zeng-Miao
authors.initials: ZM
authors.lastname: Sun
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Clinical Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Zi-Ran
authors.initials: ZR
authors.lastname: Zhao
authors.affiliation: Department of Clinical Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Zi-Tong
authors.initials: ZT
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Zi-Yuan
authors.initials: ZY
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yu-Da
authors.initials: YD
authors.lastname: Zhao
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Cheng-Cheng
authors.initials: CC
authors.lastname: Zhou
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Yao
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Su-Ya
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Department of Clinical Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Bai-Hua
authors.initials: BH
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jing-Si
authors.initials: JS
authors.lastname: Dong
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Pathology, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Feng
authors.affiliation: Department of Pathology, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Su-Sheng
authors.initials: SS
authors.lastname: Shi
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Feng-Wei
authors.initials: FW
authors.lastname: Tan
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Qiu
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Shao
authors.affiliation: Department of Thoracic Surgery, Peking University Cancer Hospital, Beijing, China.
authors.forename: Li-Jian
authors.initials: LJ
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Lan-Jun
authors.initials: LJ
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xue
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Shu-Geng
authors.initials: SG
authors.lastname: Gao
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: He
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D059472:Exome / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011379:Prognosis; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics; D016019:Survival Analysis