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

Author:

Tang Ming,Abbas Hussein A.ORCID,Negrao Marcelo V.ORCID,Ramineni Maheshwari,Hu Xin,Hubert Shawna MarieORCID,Fujimoto Junya,Reuben AlexandreORCID,Varghese Susan,Zhang JianhuaORCID,Li Jun,Chow Chi-Wan,Mao Xizeng,Song Xingzhi,Lee Won-Chul,Wu JiaORCID,Little Latasha,Gumbs Curtis,Behrens Carmen,Moran CesarORCID,Weissferdt Annikka,Lee J. JackORCID,Sepesi Boris,Swisher StephenORCID,Cheng ChaoORCID,Kurie JonathanORCID,Gibbons DonORCID,Heymach John V.ORCID,Wistuba Ignacio I.,Futreal P. AndrewORCID,Kalhor NedaORCID,Zhang JianjunORCID

Abstract

AbstractHistology 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.

Publisher

Springer Science and Business Media LLC

Subject

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

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