- Main
Whole-genome characterization of lung adenocarcinomas lacking the RTK/RAS/RAF pathway.
- Author(s): 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 AA
- 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, JC
- 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
- et al.
Published Web Location
https://doi.org/10.1016/j.celrep.2021.108707Abstract
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.
Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.