| Literature DB >> 25151357 |
Yi-Bo Gao1, Zhao-Li Chen1, Jia-Gen Li1, Xue-Da Hu1, Xue-Jiao Shi1, Zeng-Miao Sun1, Fan Zhang1, Zi-Ran Zhao2, Zi-Tong Li2, Zi-Yuan Liu1, Yu-Da Zhao1, Jian Sun1, Cheng-Cheng Zhou1, Ran Yao1, Su-Ya Wang1, Pan Wang2, Nan Sun1, Bai-Hua Zhang1, Jing-Si Dong1, Yue Yu1, Mei Luo1, Xiao-Li Feng3, Su-Sheng Shi3, Fang Zhou1, Feng-Wei Tan1, Bin Qiu1, Ning Li1, Kang Shao1, Li-Jian Zhang4, Lan-Jun Zhang5, Qi Xue1, Shu-Geng Gao1, Jie He1.
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.Entities:
Mesh：
Year: 2014 PMID： 25151357 DOI： 10.1038/ng.3076
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330