Whole-genome characterization of lung adenocarcinomas lacking the RTK/RAS/RAF pathway.
Jian Carrot-Zhang, Xiaotong Yao, Siddhartha Devarakonda, Aditya Deshpande, Jeffrey S Damrauer, Tiago Chedraoui Silva, Christopher K Wong, Hyo Young Choi, Ina Felau, A Gordon Robertson, Mauro A A Castro, Lisui Bao, Esther Rheinbay, Eric Minwei Liu, Tuan Trieu, David Haan, Christina Yau, Toshinori Hinoue, Yuexin Liu, Ofer Shapira, Kiran Kumar, Karen L Mungall, Hailei Zhang, Jake June-Koo Lee, Ashton Berger, Galen F Gao, Binyamin Zhitomirsky, Wen-Wei Liang, Meng Zhou, Sitapriya Moorthi, Alice H Berger, Eric A Collisson, Michael C Zody, Li Ding, Andrew D Cherniack, Gad Getz, Olivier Elemento, Christopher C Benz, Josh Stuart, J C Zenklusen, Rameen Beroukhim, Jason C Chang, Joshua D Campbell, D Neil Hayes, Lixing Yang, Peter W Laird, John N Weinstein, David J Kwiatkowski, Ming S Tsao, William D Travis, Ekta Khurana, Benjamin P Berman, Katherine A Hoadley, Nicolas Robine, TCGA Research Network, Matthew Meyerson, Ramaswamy Govindan, Marcin Imielinski
Cell reports 2021 Feb 02RTK/RAS/RAF pathway alterations (RPAs) are a hallmark of lung adenocarcinoma (LUAD). In this study, we use whole-genome sequencing (WGS) of 85 cases found to be RPA(-) by previous studies from The Cancer Genome Atlas (TCGA) to characterize the minority of LUADs lacking apparent alterations in this pathway. We show that WGS analysis uncovers RPA(+) in 28 (33%) of the 85 samples. Among the remaining 57 cases, we observe focal deletions targeting the promoter or transcription start site of STK11 (n = 7) or KEAP1 (n = 3), and promoter mutations associated with the increased expression of ILF2 (n = 6). We also identify complex structural variations associated with high-level copy number amplifications. Moreover, an enrichment of focal deletions is found in TP53 mutant cases. Our results indicate that RPA(-) cases demonstrate tumor suppressor deletions and genome instability, but lack unique or recurrent genetic lesions compensating for the lack of RPAs. Larger WGS studies of RPA(-) cases are required to understand this important LUAD subset. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Citation
Jian Carrot-Zhang, Xiaotong Yao, Siddhartha Devarakonda, Aditya Deshpande, Jeffrey S Damrauer, Tiago Chedraoui Silva, Christopher K Wong, Hyo Young Choi, Ina Felau, A Gordon Robertson, Mauro A A Castro, Lisui Bao, Esther Rheinbay, Eric Minwei Liu, Tuan Trieu, David Haan, Christina Yau, Toshinori Hinoue, Yuexin Liu, Ofer Shapira, Kiran Kumar, Karen L Mungall, Hailei Zhang, Jake June-Koo Lee, Ashton Berger, Galen F Gao, Binyamin Zhitomirsky, Wen-Wei Liang, Meng Zhou, Sitapriya Moorthi, Alice H Berger, Eric A Collisson, Michael C Zody, Li Ding, Andrew D Cherniack, Gad Getz, Olivier Elemento, Christopher C Benz, Josh Stuart, J C Zenklusen, Rameen Beroukhim, Jason C Chang, Joshua D Campbell, D Neil Hayes, Lixing Yang, Peter W Laird, John N Weinstein, David J Kwiatkowski, Ming S Tsao, William D Travis, Ekta Khurana, Benjamin P Berman, Katherine A Hoadley, Nicolas Robine, TCGA Research Network, Matthew Meyerson, Ramaswamy Govindan, Marcin Imielinski. Whole-genome characterization of lung adenocarcinomas lacking the RTK/RAS/RAF pathway. Cell reports. 2021 Feb 02;34(5):108707
Mesh Tags
Substances
PMID: 33535033
View Full Text
