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National Institute of Environmental Health Sciences

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Publication Detail

Title: Whole-genome characterization of lung adenocarcinomas lacking the RTK/RAS/RAF pathway.

Authors: Carrot-Zhang, Jian; Yao, Xiaotong; Devarakonda, Siddhartha; Deshpande, Aditya; Damrauer, Jeffrey S; Silva, Tiago Chedraoui; Wong, Christopher K; Choi, Hyo Young; Felau, Ina; Robertson, A Gordon; Castro, Mauro A A; Bao, Lisui; Rheinbay, Esther; Liu, Eric Minwei; Trieu, Tuan; Haan, David; Yau, Christina; Hinoue, Toshinori; Liu, Yuexin; Shapira, Ofer; Kumar, Kiran; Mungall, Karen L; Zhang, Hailei; Lee, Jake June-Koo; Berger, Ashton; Gao, Galen F; Zhitomirsky, Binyamin; Liang, Wen-Wei; Zhou, Meng; Moorthi, Sitapriya; Berger, Alice H; Collisson, Eric A; Zody, Michael C; Ding, Li; Cherniack, Andrew D; Getz, Gad; Elemento, Olivier; Benz, Christopher C; Stuart, Josh; Zenklusen, J C; Beroukhim, Rameen; Chang, Jason C; Campbell, Joshua D; Hayes, D Neil; Yang, Lixing; Laird, Peter W; Weinstein, John N; Kwiatkowski, David J; Tsao, Ming S; Travis, William D; Khurana, Ekta; Berman, Benjamin P; Hoadley, Katherine A; Robine, Nicolas; TCGA Research Network; Meyerson, Matthew; Govindan, Ramaswamy; Imielinski, Marcin

Published In Cell Rep, (2021 02 02)

Abstract: RTK/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.

PubMed ID: 33535033 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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