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The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics

Author

Listed:
  • Ming Tang

    (The University of Texas MD Anderson Cancer Center)

  • Hussein A. Abbas

    (The University of Texas MD Anderson Cancer Center)

  • Marcelo V. Negrao

    (The University of Texas MD Anderson Cancer Center)

  • Maheshwari Ramineni

    (Baylor College of Medicine)

  • Xin Hu

    (The University of Texas MD Anderson Cancer Center)

  • Shawna Marie Hubert

    (The University of Texas MD Anderson Cancer Center)

  • Junya Fujimoto

    (The University of Texas MD Anderson Cancer Center)

  • Alexandre Reuben

    (The University of Texas MD Anderson Cancer Center)

  • Susan Varghese

    (The University of Texas MD Anderson Cancer Center)

  • Jianhua Zhang

    (The University of Texas MD Anderson Cancer Center)

  • Jun Li

    (The University of Texas MD Anderson Cancer Center)

  • Chi-Wan Chow

    (The University of Texas MD Anderson Cancer Center)

  • Xizeng Mao

    (The University of Texas MD Anderson Cancer Center)

  • Xingzhi Song

    (The University of Texas MD Anderson Cancer Center)

  • Won-Chul Lee

    (The University of Texas MD Anderson Cancer Center)

  • Jia Wu

    (The University of Texas MD Anderson Cancer Center)

  • Latasha Little

    (The University of Texas MD Anderson Cancer Center)

  • Curtis Gumbs

    (The University of Texas MD Anderson Cancer Center)

  • Carmen Behrens

    (The University of Texas MD Anderson Cancer Center)

  • Cesar Moran

    (The University of Texas MD Anderson Cancer Center)

  • Annikka Weissferdt

    (The University of Texas MD Anderson Cancer Center)

  • J. Jack Lee

    (The University of Texas MD Anderson Cancer Center)

  • Boris Sepesi

    (The University of Texas MD Anderson Cancer Center)

  • Stephen Swisher

    (The University of Texas MD Anderson Cancer Center)

  • Chao Cheng

    (Baylor College of Medicine)

  • Jonathan Kurie

    (The University of Texas MD Anderson Cancer Center)

  • Don Gibbons

    (The University of Texas MD Anderson Cancer Center)

  • John V. Heymach

    (The University of Texas MD Anderson Cancer Center)

  • Ignacio I. Wistuba

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • P. Andrew Futreal

    (The University of Texas MD Anderson Cancer Center)

  • Neda Kalhor

    (The University of Texas MD Anderson Cancer Center)

  • Jianjun Zhang

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

Abstract

Histology plays an essential role in therapeutic decision-making for lung cancer patients. However, the molecular determinants of lung cancer histology are largely unknown. We conduct whole-exome sequencing and microarray profiling on 19 micro-dissected tumor regions of different histologic subtypes from 9 patients with lung cancers of mixed histology. A median of 68.9% of point mutations and 83% of copy number aberrations are shared between different histologic components within the same tumors. Furthermore, different histologic components within the tumors demonstrate similar subclonal architecture. On the other hand, transcriptomic profiling reveals shared pathways between the same histologic subtypes from different patients, which is supported by the analyses of the transcriptomic data from 141 cell lines and 343 lung cancers of different histologic subtypes. These data derived from mixed histologic subtypes in the setting of identical genetic background and exposure history support that the histologic fate of lung cancer cells is associated with transcriptomic features rather than the genomic profiles in most tumors.

Suggested Citation

  • Ming Tang & Hussein A. Abbas & Marcelo V. Negrao & Maheshwari Ramineni & Xin Hu & Shawna Marie Hubert & Junya Fujimoto & Alexandre Reuben & Susan Varghese & Jianhua Zhang & Jun Li & Chi-Wan Chow & Xiz, 2021. "The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27341-1
    DOI: 10.1038/s41467-021-27341-1
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    as
    1. Jordi Barretina & Giordano Caponigro & Nicolas Stransky & Kavitha Venkatesan & Adam A. Margolin & Sungjoon Kim & Christopher J.Wilson & Joseph Lehár & Gregory V. Kryukov & Dmitriy Sonkin & Anupama Red, 2012. "Addendum: The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity," Nature, Nature, vol. 492(7428), pages 290-290, December.
    2. Jordi Barretina & Giordano Caponigro & Nicolas Stransky & Kavitha Venkatesan & Adam A. Margolin & Sungjoon Kim & Christopher J. Wilson & Joseph Lehár & Gregory V. Kryukov & Dmitriy Sonkin & Anupama Re, 2012. "The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity," Nature, Nature, vol. 483(7391), pages 603-607, March.
    3. Yu Liu & Jianjun Zhang & Lin Li & Guangliang Yin & Jianhua Zhang & Shan Zheng & Hannah Cheung & Ning Wu & Ning Lu & Xizeng Mao & Longhai Yang & Jiexin Zhang & Li Zhang & Sahil Seth & Huang Chen & Xing, 2016. "Genomic heterogeneity of multiple synchronous lung cancer," Nature Communications, Nature, vol. 7(1), pages 1-8, December.
    4. Ludmil B. Alexandrov & Serena Nik-Zainal & David C. Wedge & Samuel A. J. R. Aparicio & Sam Behjati & Andrew V. Biankin & Graham R. Bignell & Niccolò Bolli & Ake Borg & Anne-Lise Børresen-Dale & Sandri, 2013. "Correction: Corrigendum: Signatures of mutational processes in human cancer," Nature, Nature, vol. 502(7470), pages 258-258, October.
    5. Floris P. Barthel & Kevin C. Johnson & Frederick S. Varn & Anzhela D. Moskalik & Georgette Tanner & Emre Kocakavuk & Kevin J. Anderson & Olajide Abiola & Kenneth Aldape & Kristin D. Alfaro & Donat Alp, 2019. "Longitudinal molecular trajectories of diffuse glioma in adults," Nature, Nature, vol. 576(7785), pages 112-120, December.
    6. Matthew J. Niederst & Lecia V. Sequist & John T. Poirier & Craig H. Mermel & Elizabeth L. Lockerman & Angel R. Garcia & Ryohei Katayama & Carlotta Costa & Kenneth N. Ross & Teresa Moran & Emily Howe &, 2015. "RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer," Nature Communications, Nature, vol. 6(1), pages 1-10, May.
    7. Xin Hu & Junya Fujimoto & Lisha Ying & Junya Fukuoka & Kazuto Ashizawa & Wenyong Sun & Alexandre Reuben & Chi-Wan Chow & Nicholas McGranahan & Runzhe Chen & Jinlin Hu & Myrna C. Godoy & Kazuhiro Tabat, 2019. "Multi-region exome sequencing reveals genomic evolution from preneoplasia to lung adenocarcinoma," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    8. Ludmil B. Alexandrov & Serena Nik-Zainal & David C. Wedge & Samuel A. J. R. Aparicio & Sam Behjati & Andrew V. Biankin & Graham R. Bignell & Niccolò Bolli & Ake Borg & Anne-Lise Børresen-Dale & Sandri, 2013. "Signatures of mutational processes in human cancer," Nature, Nature, vol. 500(7463), pages 415-421, August.
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