Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamous cell carcinoma

被引：226

作者：

Hao, Jia-Jie ^{[1
,2
]}

Lin, De-Chen ^{[3
,4
]}

Dinh, Huy Q. ^{[5
]}

Mayakonda, Anand ^{[6
]}

Jiang, Yan-Yi ^{[6
]}

Chang, Chen ^{[1
,2
]}

Jiang, Ye ^{[1
,2
]}

Lu, Chen-Chen ^{[1
,2
]}

Shi, Zhi-Zhou ^{[7
]}

Xu, Xin ^{[1
,2
]}

Zhang, Yu ^{[1
,2
]}

Cai, Yan ^{[1
,2
]}

Wang, Jin-Wu ^{[8
]}

Zhan, Qi-Min ^{[1
,2
]}

Wei, Wen-Qiang ^{[2
,9
]}

Berrnan, Benjamin P. ^{[5
]}

Wang, Ming-Rong ^{[1
,2
]}

Koeffler, H. Phillip ^{[3
,6
,10
]}

机构：

[1] Chinese Acad Med Sci, Natl Canc Ctr, Canc Hosp, State Key Lab Mol Oncol, Beijing, Peoples R China

[2] Peking Union Med Coll, Beijing, Peoples R China

[3] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Div Hematol Oncol, Los Angeles, CA 90048 USA

[4] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Med Res Ctr, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou, Guangdong, Peoples R China

[5] Cedars Sinai Med Ctr, Biomed Sci, Ctr Bioinformat & Funct Genom, Los Angeles, CA 90048 USA

[6] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore, Singapore

[7] Kunming Univ Sci & Technol, Fac Med, Kunming, Peoples R China

[8] Linzhou Canc Hosp, Dept Pathol, Linzhou, Henan, Peoples R China

[9] Chinese Acad Med Sci, Natl Canc Ctr, Canc Hosp, Dept Canc Epidemiol, Beijing, Peoples R China

[10] Natl Univ Singapore, Inst Canc, Natl Univ Singapore Hosp, Singapore, Singapore

来源：

NATURE GENETICS | 2016年 / 48卷 / 12期

基金：

中国国家自然科学基金; 新加坡国家研究基金会; 北京市自然科学基金; 英国医学研究理事会;

关键词：

DNA METHYLATION; TUMOR-SUPPRESSOR; MUTATIONAL PROCESSES; CANCER; HYPERMETHYLATION; ADENOCARCINOMA; TUMORIGENESIS; PROGRESSION; METASTASIS; SIGNATURES;

D O I：

10.1038/ng.3683

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Esophageal squamous cell carcinoma (ESCC) is among the most common malignancies, but little is known about its spatial intratumoral heterogeneity (ITH) and temporal clonal evolutionary processes. To address this, we performed multiregion whole-exome sequencing on 51 tumor regions from 13 ESCC cases and multiregion global methylation profiling for 3 of these 13 cases. We found an average of 35.8% heterogeneous somatic mutations with strong evidence of ITH. Half of the driver mutations located on the branches of tumor phylogenetic trees targeted oncogenes, including PIK3CA, NFE2L2 and MTOR, among others. By contrast, the majority of truncal and clonal driver mutations occurred in tumor-suppressor genes, including TP53, KMT2D and ZNF750, among others. Interestingly, phyloepigenetic trees robustly recapitulated the topological structures of the phylogenetic trees, indicating a possible relationship between genetic and epigenetic alterations. Our integrated investigations of spatial ITH and clonal evolution provide an important molecular foundation for enhanced understanding of tumorigenesis and progression in ESCC.

引用

页码：1500 / 1507

页数：8

共 53 条

[1]

Epigenomic program of Barrett's-associated neoplastic progression reveals possible involvement of insulin signaling pathways [J].

Agarwal, Rachana ;

Jin, Zhe ;

Yang, Jian ;

Mori, Yuriko ;

Song, Jee Hoon ;

Kumar, Sahil ;

Sato, Masato ;

Cheng, Yulan ;

Olaru, Alexandru V. ;

Abraham, John M. ;

Verma, Amit ;

Meltzer, Stephen J. .

[2]

Comparative Genomic Analysis of Esophageal Adenocarcinoma and Squamous Cell Carcinoma [J].

Agrawal, Nishant ;

Jiao, Yuchen ;

Bettegowda, Chetan ;

Hutfless, Susan M. ;

Wang, Yuxuan ;

David, Stefan ;

Cheng, Yulan ;

Twaddell, William S. ;

Latt, Nyan L. ;

Shin, Eun J. ;

Wang, Li-Dong ;

Wang, Liang ;

Yang, Wancai ;

Velculescu, Victor E. ;

Vogelstein, Bert ;

Papadopoulos, Nickolas ;

Kinzler, Kenneth W. ;

Meltzer, Stephen J. .

CANCER DISCOVERY, 2012, 2 (10) :899-905

[3]

Signatures of mutational processes in human cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Aparicio, Samuel A. J. R. ;

Behjati, Sam ;

Biankin, Andrew V. ;

Bignell, Graham R. ;

Bolli, Niccolo ;

Borg, Ake ;

Borresen-Dale, Anne-Lise ;

Boyault, Sandrine ;

Burkhardt, Birgit ;

Butler, Adam P. ;

Caldas, Carlos ;

Davies, Helen R. ;

Desmedt, Christine ;

Eils, Roland ;

Eyfjord, Jorunn Erla ;

Foekens, John A. ;

Greaves, Mel ;

Hosoda, Fumie ;

Hutter, Barbara ;

Ilicic, Tomislav ;

Imbeaud, Sandrine ;

Imielinsk, Marcin ;

Jaeger, Natalie ;

Jones, David T. W. ;

Jones, David ;

Knappskog, Stian ;

Kool, Marcel ;

Lakhani, Sunil R. ;

Lopez-Otin, Carlos ;

Martin, Sancha ;

Munshi, Nikhil C. ;

Nakamura, Hiromi ;

Northcott, Paul A. ;

Pajic, Marina ;

Papaemmanuil, Elli ;

Paradiso, Angelo ;

Pearson, John V. ;

Puente, Xose S. ;

Raine, Keiran ;

Ramakrishna, Manasa ;

Richardson, Andrea L. ;

Richter, Julia ;

Rosenstiel, Philip ;

Schlesner, Matthias ;

Schumacher, Ton N. ;

Span, Paul N. ;

Teague, Jon W. .

NATURE, 2013, 500 (7463) :415-+

[4]

Widespread Hypomethylation Occurs Early and Synergizes with Gene Amplification during Esophageal Carcinogenesis [J].

Alvarez, Hector ;

Opalinska, Joanna ;

Zhou, Li ;

Sohal, Davendra ;

Fazzari, Melissa J. ;

Yu, Yiting ;

Montagna, Christina ;

Montgomery, Elizabeth A. ;

Canto, Marcia ;

Dunbar, Kerry B. ;

Wang, Jean ;

Carlos Roa, Juan ;

Mo, Yongkai ;

Bhagat, Tushar ;

Ramesh, K. H. ;

Cannizzaro, Linda ;

Mollenhauer, J. ;

Thompson, Reid F. ;

Suzuki, Masako ;

Meltzer, Stephen J. ;

Melnick, Ari ;

Greally, John M. ;

Maitra, Anirban ;

Verma, Amit .

PLOS GENETICS, 2011, 7 (03)

[5]

A decade of exploring the cancer epigenome - biological and translational implications [J].

Baylin, Stephen B. ;

Jones, Peter A. .

NATURE REVIEWS CANCER, 2011, 11 (10) :726-734

[6]

DNA methylation dynamics in health and disease [J].

Bergman, Yehudit ;

Cedar, Howard .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2013, 20 (03) :274-281

[7]

Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling [J].

Britschgi, Adrian ;

Bill, Anke ;

Brinkhaus, Heike ;

Rothwell, Christopher ;

Clay, Ieuan ;

Duss, Stephan ;

Rebhan, Michael ;

Raman, Pichai ;

Guy, Chantale T. ;

Wetzel, Kristie ;

George, Elizabeth ;

Popa, M. Oana ;

Lilley, Sarah ;

Choudhury, Hedaythul ;

Gosling, Martin ;

Wang, Louis ;

Fitzgerald, Stephanie ;

Borawski, Jason ;

Baffoe, Jonathan ;

Labow, Mark ;

Gaither, L. Alex ;

Bentires-Alj, Mohamed .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (11) :E1026-E1034

[8]

Intratumor DNA Methylation Heterogeneity Reflects Clonal Evolution in Aggressive Prostate Cancer [J].

Brocks, David ;

Assenov, Yassen ;

Minner, Sarah ;

Bogatyrova, Olga ;

Simon, Ronald ;

Koop, Christina ;

Oakes, Christopher ;

Zucknick, Manuela ;

Lipka, Daniel Bernhard ;

Weischenfeldt, Joachim ;

Feuerbach, Lars ;

Lari, Richard Cowper-Sal ;

Lupien, Mathieu ;

Brors, Benedikt ;

Korbel, Jan ;

Schlomm, Thorsten ;

Tanay, Amos ;

Sauter, Guido ;

Gerhaeuser, Clarissa ;

Plass, Christoph .

CELL REPORTS, 2014, 8 (03) :798-806

[9]

Multiple region whole-exome sequencing reveals dramatically evolving intratumor genomic heterogeneity in esophageal squamous cell carcinoma [J].

Cao, W. ;

Wu, W. ;

Yan, M. ;

Tian, F. ;

Ma, C. ;

Zhang, Q. ;

Li, X. ;

Han, P. ;

Liu, Z. ;

Gu, J. ;

Biddle, F. G. .

ONCOGENESIS, 2015, 4 :e175-e175

[10]

Whole-Genome Sequencing Reveals Diverse Models of Structural Variations in Esophageal Squamous Cell Carcinoma [J].

Cheng, Caixia ;

Zhou, Yong ;

Li, Hongyi ;

Xiong, Teng ;

Li, Shuaicheng ;

Bi, Yanghui ;

Kong, Pengzhou ;

Wang, Fang ;

Cui, Heyang ;

Li, Yaoping ;

Fang, Xiaodong ;

Yan, Ting ;

Li, Yike ;

Wang, Juan ;

Yang, Bin ;

Zhang, Ling ;

Jia, Zhiwu ;

Song, Bin ;

Hu, Xiaoling ;

Yang, Jie ;

Qiu, Haile ;

Zhang, Gehong ;

Liu, Jing ;

Xu, Enwei ;

Shi, Ruyi ;

Zhang, Yanyan ;

Liu, Haiyan ;

He, Chanting ;

Zhao, Zhenxiang ;

Qian, Yu ;

Rong, Ruizhou ;

Han, Zhiwei ;

Zhang, Yanlin ;

Luo, Wen ;

Wang, Jiaqian ;

Peng, Shaoliang ;

Yang, Xukui ;

Li, Xiangchun ;

Li, Lin ;

Fang, Hu ;

Liu, Xingmin ;

Ma, Li ;

Chen, Yunqing ;

Guo, Shiping ;

Chen, Xing ;

Xi, Yanfeng ;

Li, Guodong ;

Liang, Jianfang ;

Yang, Xiaofeng ;

Guo, Jiansheng .

AMERICAN JOURNAL OF HUMAN GENETICS, 2016, 98 (02) :256-274

← 1 2 3 4 5 6 →