The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics
Ming Tang, Hussein A. Abbas, Marcelo V. Negrão, Maheshwari Ramineni, Xin Hu, Shawna M. 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, César A. Moran, Annikka Weissferdt, J. Jack Lee, Boris Sepesi, Stephen G. Swisher, Chao Cheng, Jonathan M. Kurie, Don L. Gibbons, John V. Heymach, Ignacio I. Wistuba, P. Andrew Futreal, Neda Kalhor, Jianjun Zhang, Jianjun Zhang, Jianjun Zhang
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.