Whole-genome sequencing of 508 patients identifies key molecular features associated with poor prognosis in esophageal squamous cell carcinoma.

作者：Cui, Yongping; Chen, Hongyan; Xi, Ruibin; Cui, Heyang; Zhao, Yahui; Xu, Enwei; Yan, Ting; Lu, Xiaomei; Huang, Furong; Kong, Pengzhou; Li, Yang; Zhu, Xiaolin; Wang, Jiawei; Zhu, Wenjie; Wang, Jie; Ma, Yanchun; Zhou, Yong; Guo, Shiping; Zhang, Ling; Liu, Yiqian; Wang, Bin; Xi, Yanfeng; Sun, Ruifang; Yu, Xiao; Zhai, Yuanfang; Wang, Fang; Yang, Jian; Yang, Bin; Cheng, Caixia; Liu, Jing; Song, Bin; Li, Hongyi; Wang, Yi; Zhang, Yingchun; Cheng, Xiaolong; Zhan, Qimin^*; Li, Yanhong

来源：Cell Research, 2020, 30(10): 902-913.

DOI：10.1038/s41422-020-0333-6

Esophageal squamous cell carcinoma (ESCC) is a poor-prognosis cancer type with limited understanding of its molecular etiology. Using 508 ESCC genomes, we identified five novel significantly mutated genes and uncovered mutational signature clusters associated with metastasis and patients' outcomes. Several functional assays implicated that NFE2L2 may act as a tumor suppressor in ESCC and that mutations in NFE2L2 probably impaired its tumor-suppressive function, or even conferred oncogenic activities. Additionally, we found that the NFE2L2 mutations were significantly associated with worse prognosis of ESCC. We also identified potential noncoding driver mutations including hotspot mutations in the promoter region of SLC35E2 that were correlated with worse survival. Approximately 5.9% and 15.2% of patients had high tumor mutation burden or actionable mutations, respectively, and may benefit from immunotherapy or targeted therapies. We found clinically relevant coding and noncoding genomic alterations and revealed three major subtypes that robustly predicted patients' outcomes. Collectively, we report the largest dataset of genomic profiling of ESCC useful for developing ESCC-specific biomarkers for diagnosis and treatment.

• 单位
  山西省肿瘤医院; 中国医学科学院; 香港科技大学; The Hong Kong University of Science & Technology; the Hong Kong University of Science and Technology