Journal Article

Genetic landscape of esophageal squamous cell carcinoma

Wang, Pan, Qiu, Bin, Li, Jia-Gen, Zhao, Yu-Da, Zhang, Bai-Hua, Li, Zi-Tong, Yao, Ran, Zhou, Cheng-Cheng, Zhou, Fang, Zhang, Lan-Jun, Gao, Yi-Bo, Yu, Yue, Zhang, Li-Jian, Wang, Su-Ya, Feng, Xiao-Li, He, Jie, Li, Ning, Shi, Xue-Jiao, Sun, Zeng-Miao, Gao, Shu-Geng, Tan, Feng-Wei, Zhang, Fan, Sun, Jian, Shi, Su-Sheng, Luo, Mei, Hu, Xue-Da, Sun, Nan, Dong, Jing-Si, Chen, Zhao-Li, Zhao, Zi-Ran, Shao, Kang, Xue, Qi, Liu, Zi-Yuan

2014

Overview

Jie He and colleagues report exome sequencing of 113 tumor-normal pairs of esophageal squamous cell carcinoma. They highlight mutations in genes involved in cell cycle and apoptosis regulation, histone modifier genes and genes encoding members of the Hippo and Notch pathways. Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers 1 . 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 13/109 / 13/44 / 13/51 / 13/89 / 14/1 / 14/10 / 14/105 / 14/63 / 38/22 / 38/23 / 38/70 / 38/77 / 38/90 / 45/41 / 45/47 / 631/208/514/1948 / 692/699/67/1504/1477 / Agriculture / Animal Genetics and Genomics / Apoptosis - genetics / Biomedical and Life Sciences / Biomedicine / Cancer Research / Carcinoma, Squamous Cell - genetics / Carcinoma, Squamous Cell - pathology / Cell cycle / Cell Cycle - genetics / Cell Line, Tumor / Deoxyribonucleic acid / DNA / DNA repair / Epigenesis, Genetic - genetics / Esophageal cancer / Esophageal Neoplasms - genetics / Esophageal Neoplasms - pathology / Exome - genetics / Gene Function / Genes / Genetic aspects / Genetic Predisposition to Disease - genetics / Genetic testing / Genomes / Genomics / Human Genetics / Humans / letter / Mutation / Prognosis / Sequence Analysis, DNA / Signal Transduction - genetics / Smoking / Squamous cell carcinoma / Studies / Survival Analysis / Thoracic surgery / Tumors