@article{1f93aa05a2cc4d40b78acd4e82c253b5,
title = "Whole-genome characterization of lung adenocarcinomas lacking the RTK/RAS/RAF pathway",
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.",
keywords = "TCGA, driver, genome analysis, lung adenocarcinoma, noncoding, oncogene, precision oncology, structural variation, tumor suppressor, whole genome sequencing",
author = "{TCGA Research Network} and Jian Carrot-Zhang and Xiaotong Yao and Siddhartha Devarakonda and Aditya Deshpande and Damrauer, {Jeffrey S.} and Silva, {Tiago Chedraoui} and Wong, {Christopher K.} and Choi, {Hyo Young} and Ina Felau and Robertson, {A. Gordon} and Castro, {Mauro A.A.} and Lisui Bao and Esther Rheinbay and Liu, {Eric Minwei} and Tuan Trieu and David Haan and Christina Yau and Toshinori Hinoue and Yuexin Liu and Ofer Shapira and Kiran Kumar and Mungall, {Karen L.} and Hailei Zhang and Lee, {Jake June Koo} and Ashton Berger and Gao, {Galen F.} and Binyamin Zhitomirsky and Liang, {Wen Wei} and Meng Zhou and Sitapriya Moorthi and Berger, {Alice H.} and Collisson, {Eric A.} and Zody, {Michael C.} and Li Ding and Cherniack, {Andrew D.} and Gad Getz and Olivier Elemento and Benz, {Christopher C.} and Josh Stuart and Zenklusen, {J. C.} and Rameen Beroukhim and Chang, {Jason C.} and Campbell, {Joshua D.} and Hayes, {D. Neil} and Lixing Yang and Laird, {Peter W.} and Weinstein, {John N.} and Kwiatkowski, {David J.} and Tsao, {Ming S.} and Ramaswamy Govindan",
note = "Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = feb,
day = "2",
doi = "10.1016/j.celrep.2021.108707",
language = "English",
volume = "34",
journal = "Cell Reports",
issn = "2639-1856",
number = "5",
}