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

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, Xizeng Mao, Xingzhi Song, Won-Chul Lee, Jia Wu, Latasha Little, Curtis Gumbs, Carmen Behrens, Cesar Moran, Annikka Weissferdt, J. Jack Lee, Boris Sepesi, Stephen Swisher, Chao Cheng, Jonathan Kurie, Don Gibbons, John V. Heymach, Ignacio I. Wistuba, P. Andrew Futreal (), Neda Kalhor () and Jianjun Zhang ()
Additional contact information
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
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

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-27341-1

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