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

TitleWhole-genome characterization of lung adenocarcinomas lacking the RTK/RAS/RAF pathway.
Publication TypeJournal Article
Year of Publication2021
AuthorsCarrot-Zhang J, Yao X, Devarakonda S, Deshpande A, Damrauer JS, Silva TChedraoui, Wong CK, Choi HYoung, Felau I, A Robertson G, Castro MAA, Bao L, Rheinbay E, Liu EMinwei, Trieu T, Haan D, Yau C, Hinoue T, Liu Y, Shapira O, Kumar K, Mungall KL, Zhang H, Lee JJune-Koo, Berger A, Gao GF, Zhitomirsky B, Liang W-W, Zhou M, Moorthi S, Berger AH, Collisson EA, Zody MC, Ding L, Cherniack AD, Getz G, Elemento O, Benz CC, Stuart J, Zenklusen JC, Beroukhim R, Chang JC, Campbell JD, D Hayes N, Yang L, Laird PW, Weinstein JN, Kwiatkowski DJ, Tsao MS, Travis WD, Khurana E, Berman BP, Hoadley KA, Robine N, Meyerson M, Govindan R, Imielinski M
Corporate AuthorsTCGA Research Network
JournalCell Rep
Volume34
Issue5
Pagination108707
Date Published2021 02 02
ISSN2211-1247
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.

DOI10.1016/j.celrep.2021.108707
Alternate JournalCell Rep
PubMed ID33535033
PubMed Central IDPMC8009291
Grant ListU24 CA210978 / CA / NCI NIH HHS / United States
U24 CA211000 / CA / NCI NIH HHS / United States
U24 CA210950 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
U24 CA210974 / CA / NCI NIH HHS / United States
U24 CA210989 / CA / NCI NIH HHS / United States
U24 CA210952 / CA / NCI NIH HHS / United States
U24 CA210949 / CA / NCI NIH HHS / United States
U24 CA143867 / CA / NCI NIH HHS / United States
U24 CA126546 / CA / NCI NIH HHS / United States
U24 CA210990 / CA / NCI NIH HHS / United States
U24 CA210957 / CA / NCI NIH HHS / United States
R35 CA197568 / CA / NCI NIH HHS / United States
U24 CA210969 / CA / NCI NIH HHS / United States
U24 CA210988 / CA / NCI NIH HHS / United States
U24 CA211006 / CA / NCI NIH HHS / United States
U24 CA210999 / CA / NCI NIH HHS / United States
Related Faculty: 
Marcin Imielinski, M.D., Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
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