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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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