Innate Genetic Evolution of Lung Cancers and Spatial Heterogeneity: Analysis of Treatment-Naive Lesions

被引：24

作者：

Suda, Kenichi ^{[1
,2
]}

Kim, Jihye ^{[1
]}

Murakami, Isao ^{[3
]}

Rozeboom, Leslie ^{[1
]}

Shimoji, Masaki ^{[2
]}

Shimizu, Shigeki ^{[4
]}

Rivard, Christopher J. ^{[1
]}

Mitsudomi, Tetsuya ^{[2
]}

Tan, Aik-Choon ^{[1
]}

Hirsch, Fred R. ^{[1
]}

机构：

[1] Univ Colorado Anschutz Med Campus, Div Med Oncol, Aurora, CO USA

[2] Kindai Univ, Fac Med, Dept Surg, Div Thorac Surg, Osaka, Japan

[3] Higashi Hiroshima Med Ctr, Dept Resp Med, Higashihiroshima, Japan

[4] Kindai Univ, Fac Med, Dept Pathol, Osaka, Japan

来源：

JOURNAL OF THORACIC ONCOLOGY | 2018年 / 13卷 / 10期

基金：

美国国家卫生研究院;

关键词：

Biomarkers; Tumor heterogeneity; RNA sequencing; Autopsy; Immune-related markers; RET fusion; ACQUIRED-RESISTANCE; KINASE INHIBITOR; READ ALIGNMENT; EGFR MUTATIONS; OPEN-LABEL; RET; FUSIONS; GENOME; ADENOCARCINOMAS; AMPLIFICATION;

D O I：

10.1016/j.jtho.2018.05.039

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Introduction: Data regarding the pre-treatment inter-tumor heterogeneity of potential biomarkers in advanced-stage lung cancers is limited. A finding of such heterogeneity between primary and metastatic lesions would prove valuable to determine if a metastatic lesion can be a surrogate for the primary tumor, as more biomarkers will likely be used in the future to inform treatment decisions. Methods: We performed RNA sequencing to analyze intertumor heterogeneity in 30 specimens (primary tumors, intrathoracic, and extrathoracic metastatic lesions) obtained from five treatment-naive lung cancer patients. Results: The global unsupervised clustering analysis showed that the lesions clustered at the individual patient level rather than on the metastatic sites, suggesting that the characteristics of specific tumor cells have a greater impact on the gene expression signature than the microenvironment in which the metastasis develops. The mutational and transcriptional data highlight the presence of intertumor heterogeneity showing that the primary tumors are usually distinct from metastatic lesions. Through a comparison between metastatic lesions and the primary tumors, we observed that pathways related to cell proliferation were upregulated, whereas immune-related pathways were downregulated in metastatic lesions. Conclusion: These data not only provide insight into the evolution of lung cancers, but also imply possibilities and limitations of biomarker-based treatment in lung cancers. (C) 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：1496 / 1507

页数：12

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共 42 条

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Adzhubei Ivan, 2013, Curr Protoc Hum Genet, VChapter 7, DOI 10.1002/0471142905.hg0720s76

[2]

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 ;

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Verma, Amit ;

Montagna, Cristina ;

Chachoua, Abraham ;

Goel, Sanjay ;

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Shan, Jidong ;

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Gritsman, Kira ;

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Creighton, Chad J. ;

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Hayes, D. Neil ;

Hernandez, Bryan ;

Herman, James G. ;

Heymach, John V. ;

Jurisica, Igor ;

Kucherlapati, Raju ;

Kwiatkowski, David ;

Ladanyi, Marc ;

Robertson, Gordon ;

Schultz, Nikolaus ;

Shen, Ronglai ;

Sinha, Rileen ;

Sougnez, Carrie ;

Tsao, Ming-Sound ;

Travis, William D. ;

Weinstein, John N. ;

Wigle, Dennis A. ;

Wilkerson, Matthew D. ;

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Cherniack, Andrew D. ;

Hadjipanayis, Angela ;

Rosenberg, Mara ;

Weisenberger, Daniel J. ;

Laird, Peter W. ;

Radenbaugh, Amie ;

Ma, Singer ;

Stuart, Joshua M. ;

Byers, Lauren Averett ;

Baylin, Stephen B. ;

Govindan, Ramaswamy ;

Meyerson, Matthew ;

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Gabriel, Stacey B. ;

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Shafi, Seema ;

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Groenroos, Eva ;

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Varela, Ignacio ;

Jones, David ;

Marshall, John ;

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Van Loo, Peter ;

Rassl, Doris M. ;

Rintoul, Robert C. ;

Janes, Sam M. ;

Lee, Siow-Ming ;

Forster, Martin ;

Ahmad, Tanya ;

Lawrence, David ;

Falzon, Mary ;

Capitanio, Arrigo ;

Harkins, Timothy T. ;

Lee, Clarence C. ;

Tom, Warren ;

Teefe, Enock ;

Chen, Shann-Ching ;

Begum, Sharmin ;

Rabinowitz, Adam ;

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Somwar, Romel ;

Smith, Roger S. ;

Montecalvo, Joseph ;

Plodkowski, Andrew ;

Ginsberg, Michelle S. ;

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Ozretic, Luka ;

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Lu, Xin ;

Fernandez-Cuesta, Lynnette ;

Bosco, Graziella ;

Mueller, Christian ;

Dahmen, Ilona ;

Jahchan, Nadine S. ;

Park, Kwon-Sik ;

Yang, Dian ;

Karnezis, Anthony N. ;

Vaka, Dedeepya ;

Torres, Angela ;

Wang, Maia Segura ;

Korbel, Jan O. ;

Menon, Roopika ;

Chun, Sung-Min ;

Kim, Deokhoon ;

Wilkerson, Matt ;

Hayes, Neil ;

Engelmann, David ;

Puetzer, Brigitte ;

Bos, Marc ;

Michels, Sebastian ;

Vlasic, Ignacija ;

Seidel, Danila ;

Pinther, Berit ;

Schaub, Philipp ;

Becker, Christian ;

Altmueller, Janine ;

Yokota, Jun ;

Kohno, Takashi ;

Iwakawa, Reika ;

Tsuta, Koji ;

Noguchi, Masayuki ;

Muley, Thomas ;

Hoffmann, Hans ;

Schnabel, Philipp A. ;

Petersen, Iver ;

Chen, Yuan ;

Soltermann, Alex ;

Tischler, Verena ;

Choi, Chang-min ;

Kim, Yong-Hee ;

Massion, Pierre P. .

NATURE, 2015, 524 (7563) :47-53

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Genomic Landscape of Non-Small Cell Lung Cancer in Smokers and Never-Smokers [J].

Govindan, Ramaswamy ;

Ding, Li ;

Griffith, Malachi ;

Subramanian, Janakiraman ;

Dees, Nathan D. ;

Kanchi, Krishna L. ;

Maher, Christopher A. ;

Fulton, Robert ;

Fulton, Lucinda ;

Wallis, John ;

Chen, Ken ;

Walker, Jason ;

McDonald, Sandra ;

Bose, Ron ;

Ornitz, David ;

Xiong, Donghai ;

You, Ming ;

Dooling, David J. ;

Watson, Mark ;

Mardis, Elaine R. ;

Wilson, Richard K. .

CELL, 2012, 150 (06) :1121-1134

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Comprehensive genomic characterization of squamous cell lung cancers [J].

Hammerman, Peter S. ;

Lawrence, Michael S. ;

Voet, Douglas ;

Jing, Rui ;

Cibulskis, Kristian ;

Sivachenko, Andrey ;

Stojanov, Petar ;

McKenna, Aaron ;

Lander, Eric S. ;

Gabriel, Stacey ;

Getz, Gad ;

Sougnez, Carrie ;

Imielinski, Marcin ;

Helman, Elena ;

Hernandez, Bryan ;

Pho, Nam H. ;

Meyerson, Matthew ;

Chu, Andy ;

Chun, Hye-Jung E. ;

Mungall, Andrew J. ;

Pleasance, Erin ;

Robertson, A. Gordon ;

Sipahimalani, Payal ;

Stoll, Dominik ;

Balasundaram, Miruna ;

Birol, Inanc ;

Butterfield, Yaron S. N. ;

Chuah, Eric ;

Coope, Robin J. N. ;

Corbett, Richard ;

Dhalla, Noreen ;

Guin, Ranabir ;

Hirst, Anhe Carrie ;

Hirst, Martin ;

Holt, Robert A. ;

Lee, Darlene ;

Li, Haiyan I. ;

Mayo, Michael ;

Moore, Richard A. ;

Mungall, Karen ;

Nip, Ka Ming ;

Olshen, Adam ;

Schein, Jacqueline E. ;

Slobodan, Jared R. ;

Tam, Angela ;

Thiessen, Nina ;

Varhol, Richard ;

Zeng, Thomas ;

Zhao, Yongjun ;

Jones, Steven J. M. .

NATURE, 2012, 489 (7417) :519-525

← 1 2 3 4 5 →