Whole-genome sequencing of 508 patients identifies key molecular features associated with poor prognosis in esophageal squamous cell carcinoma.
Whole-genome sequencing of 508 patients identifies key molecular features associated with poor prognosis in esophageal squamous cell carcinoma.
复制标题
DOI：
10.1038/s41422-020-0333-6
复制
发表时间：
2020-10
期刊：
影响因子：
44.1
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Cui Y;Chen H;Xi R;Cui H;Zhao Y;Xu E;Yan T;Lu X;Huang F;Kong P;Li Y;Zhu X;Wang J;Zhu W;Wang J;Ma Y;Zhou Y;Guo S;Zhang L;Liu Y;Wang B;Xi Y;Sun R;Yu X;Zhai Y;Wang F;Yang J;Yang B;Cheng C;Liu J;Song B;Li H;Wang Y;Zhang Y;Cheng X;Zhan Q;Li Y;Liu Z
食管鳞状细胞癌（ESCC）是一种预后不良的癌症类型，对其分子病因学的了解有限。使用 508 个 ESCC 基因组，我们确定了五个新的显着突变基因，并发现了与转移和患者结果相关的突变特征簇。多项功能测定表明，NFE2L2 可能在 ESCC 中充当肿瘤抑制因子，并且 NFE2L2 的突变可能损害其肿瘤抑制功能，甚至赋予致癌活性。此外，我们发现 NFE2L2 突变与食管鳞癌预后较差显着相关。我们还发现了潜在的非编码驱动突变，包括 SLC35E2 启动子区域的热点突变，这些突变与较差的生存率相关。大约 5.9% 和 15.2% 的患者分别具有高肿瘤突变负荷或可操作突变，可能受益于免疫治疗或靶向治疗。我们发现了临床相关的编码和非编码基因组改变，并揭示了可以稳健预测患者结果的三种主要亚型。总的来说，我们报告了最大的 ESCC 基因组分析数据集，可用于开发用于诊断和治疗的 ESCC 特异性生物标志物。
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.
登录
查看更多内容
影响因子：
24.5
作者：
Deng N;Goh LK;Wang H;Das K;Tao J;Tan IB;Zhang S;Lee M;Wu J;Lim KH;Lei Z;Goh G;Lim QY;Tan AL;Sin Poh DY;Riahi S;Bell S;Shi MM;Linnartz R;Zhu F;Yeoh KG;Toh HC;Yong WP;Cheong HC;Rha SY;Boussioutas A;Grabsch H;Rozen S;Tan P
通讯作者：
Tan P
影响因子：
30.8
作者：
Blakely CM;Watkins TBK;Wu W;Gini B;Chabon JJ;McCoach CE;McGranahan N;Wilson GA;Birkbak NJ;Olivas VR;Rotow J;Maynard A;Wang V;Gubens MA;Banks KC;Lanman RB;Caulin AF;St John J;Cordero AR;Giannikopoulos P;Simmons AD;Mack PC;Gandara DR;Husain H;Doebele RC;Riess JW;Diehn M;Swanton C;Bivona TG
通讯作者：
Bivona TG
影响因子：
64.8
作者：
Cancer Genome Atlas Research Network;Analysis Working Group: Asan University;BC Cancer Agency;Brigham and Women’s Hospital;Broad Institute;Brown University;Case Western Reserve University;Dana-Farber Cancer Institute;Duke University;Greater Poland Cancer Centre;Harvard Medical School;Institute for Systems Biology;KU Leuven;Mayo Clinic;Memorial Sloan Kettering Cancer Center;National Cancer Institute;Nationwide Children’s Hospital;Stanford University;University of Alabama;University of Michigan;University of North Carolina;University of Pittsburgh;University of Rochester;University of Southern California;University of Texas MD Anderson Cancer Center;University of Washington;Van Andel Research Institute;Vanderbilt University;Washington University;Genome Sequencing Center: Broad Institute;Washington University in St. Louis;Genome Characterization Centers: BC Cancer Agency;Broad Institute;Harvard Medical School;Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University;University of North Carolina;University of Southern California Epigenome Center;University of Texas MD Anderson Cancer Center;Van Andel Research Institute;Genome Data Analysis Centers: Broad Institute;Brown University:;Harvard Medical School;Institute for Systems Biology;Memorial Sloan Kettering Cancer Center;University of California Santa Cruz;University of Texas MD Anderson Cancer Center;Biospecimen Core Resource: International Genomics Consortium;Research Institute at Nationwide Children’s Hospital;Tissue Source Sites: Analytic Biologic Services;Asan Medical Center;Asterand Bioscience;Barretos Cancer Hospital;BioreclamationIVT;Botkin Municipal Clinic;Chonnam National University Medical School;Christiana Care Health System;Cureline;Duke University;Emory University;Erasmus University;Indiana University School of Medicine;Institute of Oncology of Moldova;International Genomics Consortium;Invidumed;Israelitisches Krankenhaus Hamburg;Keimyung University School of Medicine;Memorial Sloan Kettering Cancer Center;National Cancer Center Goyang;Ontario Tumour Bank;Peter MacCallum Cancer Centre;Pusan National University Medical School;Ribeirão Preto Medical School;St. Joseph’s Hospital &Medical Center;St. Petersburg Academic University;Tayside Tissue Bank;University of Dundee;University of Kansas Medical Center;University of Michigan;University of North Carolina at Chapel Hill;University of Pittsburgh School of Medicine;University of Texas MD Anderson Cancer Center;Disease Working Group: Duke University;Memorial Sloan Kettering Cancer Center;National Cancer Institute;University of Texas MD Anderson Cancer Center;Yonsei University College of Medicine;Data Coordination Center: CSRA Inc.;Project Team: National Institutes of Health
通讯作者：
Project Team: National Institutes of Health
影响因子：
13.6
作者：
Law EK;Sieuwerts AM;LaPara K;Leonard B;Starrett GJ;Molan AM;Temiz NA;Vogel RI;Meijer-van Gelder ME;Sweep FC;Span PN;Foekens JA;Martens JW;Yee D;Harris RS
通讯作者：
Harris RS
DOI：
10.1093/bioinformatics/btv408
发表时间：
2015-11-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Gehring JS;Fischer B;Lawrence M;Huber W
通讯作者：
Huber W