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Genetic landscape of esophageal squamous cell carcinoma.

Authors: Gao, YB  Chen, ZL  Li, JG  Hu, XD  Shi, XJ  Sun, ZM  Zhang, F  Zhao, ZR  Li, ZT  Liu, ZY  Zhao, YD  Sun, J  Zhou, CC  Yao, R  Wang, SY  Wang, P  Sun, N  Zhang, BH  Dong, JS  Yu, Y  Luo, M  Feng, XL  Shi, SS  Zhou, F  Tan, FW  Qiu, B  Li, N  Shao, K  Zhang, LJ  Zhang, LJ  Xue, Q  Gao, SG  He, J 
Citation: Gao YB, etal., Nat Genet. 2014 Oct;46(10):1097-102. doi: 10.1038/ng.3076. Epub 2014 Aug 24.
Pubmed: (View Article at PubMed) PMID:25151357
DOI: Full-text: DOI:10.1038/ng.3076

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.


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RGD Object Information
RGD ID: 9588233
Created: 2014-10-22
Species: All species
Last Modified: 2014-10-22
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.