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

Autor:	Carrot-Zhang J; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA., Yao X; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; New York Genome Center, New York, NY, USA; Tri-institutional Ph.D. Program in Computational Biology and Medicine, New York, NY, USA; Caryl and Israel Englander Institute for Precision Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Devarakonda S; Section of Medical Oncology, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA., Deshpande A; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; New York Genome Center, New York, NY, USA; Tri-institutional Ph.D. Program in Computational Biology and Medicine, New York, NY, USA; Caryl and Israel Englander Institute for Precision Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Damrauer JS; Department of Genetics, Computational Medicine Program, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Silva TC; Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Wong CK; Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA., Choi HY; University of Tennessee Health Science Center, UTHSC Center for Cancer Research, TN, USA., Felau I; National Cancer Institute, Bethesda, MD, USA., Robertson AG; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada., Castro MAA; Bioinformatics and Systems Biology Laboratory, Federal University of Paraná, Curitiba, PR, Brazil., Bao L; Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA., Rheinbay E; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Massachusetts General Hospital Cancer Center, Boston, MA, USA., Liu EM; Caryl and Israel Englander Institute for Precision Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Trieu T; Caryl and Israel Englander Institute for Precision Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Haan D; Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA., Yau C; University of California, San Francisco, San Francisco, CA, USA; Buck Institute for Research on Aging, Novato, CA, USA., Hinoue T; Van Andel Institute, Grand Rapids, MI, USA., Liu Y; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Shapira O; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Kumar K; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Mungall KL; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada., Zhang H; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Lee JJ; Harvard Medical School, Boston, MA, USA., Berger A; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Gao GF; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Zhitomirsky B; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Massachusetts General Hospital Cancer Center, Boston, MA, USA., Liang WW; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO, USA., Zhou M; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA., Moorthi S; Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Berger AH; Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Collisson EA; University of California, San Francisco, San Francisco, CA, USA., Zody MC; New York Genome Center, New York, NY, USA., Ding L; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO, USA., Cherniack AD; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Getz G; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Massachusetts General Hospital Cancer Center, Boston, MA, USA., Elemento O; Tri-institutional Ph.D. Program in Computational Biology and Medicine, New York, NY, USA; Caryl and Israel Englander Institute for Precision Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Benz CC; Buck Institute for Research on Aging, Novato, CA, USA., Stuart J; Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA., Zenklusen JC; National Cancer Institute, Bethesda, MD, USA., Beroukhim R; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA., Chang JC; Thoracic Pathology, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Campbell JD; Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA, USA., Hayes DN; University of Tennessee Health Science Center, UTHSC Center for Cancer Research, TN, USA., Yang L; Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA., Laird PW; Van Andel Institute, Grand Rapids, MI, USA., Weinstein JN; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Kwiatkowski DJ; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA., Tsao MS; Department of Pathology, University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada., Travis WD; Thoracic Pathology, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Khurana E; Caryl and Israel Englander Institute for Precision Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Berman BP; Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University, Jerusalem, Israel., Hoadley KA; Department of Genetics, Computational Medicine Program, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Robine N; New York Genome Center, New York, NY, USA., Meyerson M; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: matthew_meyerson@dfci.harvard.edu., Govindan R; Section of Medical Oncology, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA. Electronic address: rgovindan@wustl.edu., Imielinski M; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA; New York Genome Center, New York, NY, USA; Caryl and Israel Englander Institute for Precision Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. Electronic address: mai9037@med.cornell.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Feb 02; Vol. 34 (5), pp. 108707.
DOI:	10.1016/j.celrep.2021.108707
Abstrakt:	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. Competing Interests: Declaration of interests M.M. is listed as the inventor on the patent for the EGFR mutation analysis for lung cancer diagnosis licensed to LabCorp; holds research support from Bayer, Janssen, and Ono; and serves as scientific advisory board chair for OrigiMed. P.W.L. serves on the scientific advisory boards of AnchorDx and Progenity. D.J.K. has research support from Revolution Medicines and Genentech and is a consultant to AADi. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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