Esophageal squamous cell carcinoma (ESCC) is a poor-prognosis cancer type with limited understanding of its molecular etiology. Here we sequenced 508 ESCC genomes, identified six novel significantly mutated genes including RPS15 and uncovered mutational signature clusters associated with metastasis and patients’ outcome. Approximately 5.9% and 22.6% of patients had high tumor mutation burden or actionable mutations, respectively, and may benefit from immunotherapy or target therapies. We found clinically relevant coding (e.g. NFE2L2) and noncoding (e.g. SLC35E2 and CCND1) genomic alterations and revealed three major subtypes (NFE2L2 mutated, RTK-RAS amplified, and double negative) that might predict patients’ outcome. Collectively, we reported the largest genomic profiling of ESCC useful for developing ESCC-specific biomarkers for diagnosis and treatment.
Cui, Yongping and Chen, Hongyan and Xi, Ruibin and Cui, Heyang and Zhao, Yahui and Yan, Ting and Xu, Enwei and Lu, Xiaomei and Huang, Furong and Kong, Pengzhou and Li, Yang and Zhu, Xiaolin and Wang, Jiawei and Zhu, Wenjie and Wang, Jie and Ma, Yanchun and Zhou, Yong and Guo, Shiping and Zhang, Ling and Liu, Yiqian and Wang, Bin and Xi, Yanfeng and Sun, Ruifang and Yu, Xiao and Zhai, Yuanfang and Wang, Fang and Yang, Jian and Yang, Bin and Cheng, Caixia and Liu, Jing and Song, Bin and Li, Hongyi and Wang, Yi and Zhang, Yingchun and Cheng, Xiaolong and Li, Yanhong and Liu, Zhihua and Zhan, Qimin, Whole Genome Sequencing of 508 Patients Identified Key Molecular Features Associated with Poor Prognosis in Esophageal Squamous Cell Carcinoma (September 3, 2019). Available at SSRN: https://ssrn.com/abstract=3447322 or http://dx.doi.org/10.2139/ssrn.3447322
This version of the paper has not been formally peer reviewed.
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