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 MoranAnnikka 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, Jianjun Zhang

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish (US)
Article number7081
JournalNature communications
Volume12
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

MD Anderson CCSG core facilities

  • Advanced Technology Genomics Core
  • Biostatistics Resource Group
  • Tissue Biospecimen and Pathology Resource
  • Bioinformatics Shared Resource

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