ArticleCell reports2021
Whole-genome characterization of lung adenocarcinomas lacking the RTK/RAS/RAF pathway.
Erratum issuedOpen access · goldAbstract read
In one paragraph
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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19citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- SMARCA4, STK11, and KEAP1 co-inactivation associates with poor prognosis and upregulation of the TGF-β pathway in lung adenocarcinoma.Translational oncology · 2026Article
- UK Biobank whole-genome sequencing reveals robust contributions of rare variants to complex-trait heritability.Genome biology · 2026Article
- A Roadmap to Transform Lung Cancer Outcomes: Priorities in Biology, Therapeutic Innovation, Early Detection, Prevention, and Interception.Cancer discovery · 2026Review
- RAS signaling in lung adenocarcinoma is defined by lineage context and DUSP4 loss.JCI insight · 2026Article
- Passenger mutations link cellular origin and transcriptional identity in human lung adenocarcinomas.Nature genetics · 2025Article
- Refining treatment strategies for non-small cell lung cancer lacking actionable mutations: insights from multi-omics studies.British journal of cancer · 2025Review
- Characterization of Mutational Signatures in Tumors from a Large Chinese Population.Cancer research communications · 2025Article
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- APOBEC affects tumor evolution and age at onset of lung cancer in smokers.Nature communications · 2025Article
- Neotelomeres and telomere-spanning chromosomal arm fusions in cancer genomes revealed by long-read sequencing.Cell genomics · 2024Article
- The mutagenic forces shaping the genomic landscape of lung cancer in never smokers.medRxiv : the preprint server for health sciences · 2024Article
- Neotelomeres and Telomere-Spanning Chromosomal Arm Fusions in Cancer Genomes Revealed by Long-Read Sequencing.bioRxiv : the preprint server for biology · 2023Article
- Rare molecular subtypes of lung cancer.Nature reviews. Clinical oncology · 2023Review
- PROTAC therapy as a new targeted therapy for lung cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Review
- Combinatorial Inactivation of Tumor Suppressors Efficiently Initiates Lung Adenocarcinoma with Therapeutic Vulnerabilities.Cancer research · 2022Article
- Molecular Pathology of Lung Cancer.Cold Spring Harbor perspectives in medicine · 2022Review
- Genomic Profiling of Lung Adenocarcinoma in Never-Smokers.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Article
- Genomic and evolutionary classification of lung cancer in never smokers.Nature genetics · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
58 authors at 20 institutions in 4 countries.
Jian Carrot-ZhangDana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
Xiaotong YaoDepartment 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.
Siddhartha DevarakondaSection 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.
Aditya DeshpandeDepartment 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.
Jeffrey S DamrauerDepartment of Genetics, Computational Medicine Program, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Tiago Chedraoui SilvaCenter for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Christopher K WongDepartment of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA.
Hyo Young ChoiUniversity of Tennessee Health Science Center, UTHSC Center for Cancer Research, TN, USA.
Ina FelauNational Cancer Institute, Bethesda, MD, USA.
A Gordon RobertsonCanada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada.
Mauro A A CastroBioinformatics and Systems Biology Laboratory, Federal University of Paraná, Curitiba, PR, Brazil.
Lisui BaoBen May Department for Cancer Research, University of Chicago, Chicago, IL, USA.
Esther RheinbayBroad Institute of MIT and Harvard, Cambridge, MA, USA; Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Eric Minwei LiuCaryl and Israel Englander Institute for Precision Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Tuan TrieuCaryl and Israel Englander Institute for Precision Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
David HaanDepartment of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA.
Christina YauUniversity of California, San Francisco, San Francisco, CA, USA; Buck Institute for Research on Aging, Novato, CA, USA.
Toshinori HinoueVan Andel Institute, Grand Rapids, MI, USA.
Yuexin LiuDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ofer ShapiraBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Kiran KumarDana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Karen L MungallCanada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada.
Hailei ZhangBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Jake June-Koo LeeHarvard Medical School, Boston, MA, USA.
Ashton BergerBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Galen F GaoBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Binyamin ZhitomirskyBroad Institute of MIT and Harvard, Cambridge, MA, USA; Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Wen-Wei LiangSiteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO, USA.
Meng ZhouDana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA.
Sitapriya MoorthiFred Hutchinson Cancer Research Center, Seattle, WA, USA.
Alice H BergerFred Hutchinson Cancer Research Center, Seattle, WA, USA.
Eric A CollissonUniversity of California, San Francisco, San Francisco, CA, USA.
Michael C ZodyNew York Genome Center, New York, NY, USA.
Li DingSiteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA; McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO, USA.
Andrew D CherniackDana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Gad GetzBroad Institute of MIT and Harvard, Cambridge, MA, USA; Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Olivier ElementoTri-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.
Christopher C BenzBuck Institute for Research on Aging, Novato, CA, USA.
Josh StuartDepartment of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA, USA.
J C ZenklusenNational Cancer Institute, Bethesda, MD, USA.
Rameen BeroukhimDana-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.
Jason C ChangThoracic Pathology, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Joshua D CampbellDivision of Computational Biomedicine, Boston University School of Medicine, Boston, MA, USA.
D Neil HayesUniversity of Tennessee Health Science Center, UTHSC Center for Cancer Research, TN, USA.
Lixing YangBen May Department for Cancer Research, University of Chicago, Chicago, IL, USA.
Peter W LairdVan Andel Institute, Grand Rapids, MI, USA.
John N WeinsteinDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
David J KwiatkowskiDepartment of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Ming S TsaoDepartment of Pathology, University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada.
William D TravisThoracic Pathology, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Ekta KhuranaCaryl and Israel Englander Institute for Precision Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Benjamin P BermanCenter 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.
Katherine A HoadleyDepartment of Genetics, Computational Medicine Program, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nicolas RobineNew York Genome Center, New York, NY, USA.
TCGA Research Network
Matthew MeyersonDana-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.
Ramaswamy GovindanSection 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.
Marcin ImielinskiDepartment 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.
Broad Institute · USCornell University · USUniversity of Chicago · USCedars-Sinai Medical Center · USThe University of Texas MD Anderson Cancer Center · USUniversity of California, Santa Cruz · USWashington University in St. Louis · USBuck Institute for Research on Aging · USCanada's Michael Smith Genome Sciences Centre · CAJames S. McDonnell Foundation · USMemorial Sloan Kettering Cancer Center · USNational Cancer Institute · USNew York Genome Center · USUniversity of North Carolina at Chapel Hill · USUniversity of Tennessee Health Science Center · USVan Andel Institute · USBoston University · USBrigham and Women's Hospital · USFred Hutch Cancer Center · USHarvard University · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MUNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Stephanie Engel · 2001 to 2026
$36.3MGenome Characterization Center (GCC)U24CA143867 · NCI · BROAD INSTITUTE, INC. · PI GABRIEL, STACEY, MEYERSON, MATTHEW L. · 2009 to 2016
$17.0MNKX2-1 Enhancer Amplification and Lineage Addiction in Lung AdenocarcinomaR35CA197568 · NCI · DANA-FARBER CANCER INST · PI Matthew L. Meyerson · 2015 to 2026
$12.4MCenter for Cancer Genome CharacterizationU24CA126546 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MEYERSON, MATTHEW L. · 2006 to 2009
$7.7MPredicting the functional impact of non-coding mutations using patient-specific gene regulatory networksR01CA218668 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI EKTA KHURANA, Neville Sanjana · 2018 to 2026
$4.7MGlobal Infrastructure for Collaborative High-throughput Cancer Genomics AnalysisU24CA210999 · NCI · BROAD INSTITUTE, INC. · PI GETZ, GAD A · 2016 to 2020
$4.7MVisualization hub for genomics data exploration and translational discoveryU24CA210974 · NCI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI COLLISSON, ERIC, HAUSSLER, DAVID H · 2016 to 2020
$4.2MIntegrative Cancer Epigenomic Data Analysis Center (ICE-DAC)U24CA210969 · NCI · VAN ANDEL RESEARCH INSTITUTE · PI LAIRD, PETER W · 2016 to 2020
$2.5MThe joint WCM-NYGC Center for Functional and Clinical Interpretation of Tumor ProfilesU24CA210989 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI ELEMENTO, OLIVIER, ZODY, MICHAEL C · 2016 to 2020
$2.4MCenter for the comprehensive analysis of somatic copy-number alterations in cancerU24CA210978 · NCI · BROAD INSTITUTE, INC. · PI BEROUKHIM, RAMEEN, CHERNIACK, ANDREW DAVID · 2016 to 2020
$2.3MUCSC-Buck Specialized Genomic Data Analysis Center for the Genomic Data Analysis NetworkU24CA210990 · NCI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI STUART, JOSHUA MICHAEL · 2016 to 2020
$2.2MNCI NIH HHS P30 CA008748NCI NIH HHS R01 CA218668NCI NIH HHS R35 CA197568NCI NIH HHS U24 CA126546NCI NIH HHS U24 CA143867NCI NIH HHS U24 CA210949NCI NIH HHS U24 CA210950NCI NIH HHS U24 CA210952NCI NIH HHS U24 CA210957NCI NIH HHS U24 CA210969NCI NIH HHS U24 CA210974NCI NIH HHS U24 CA210978NCI NIH HHS U24 CA210988NCI NIH HHS U24 CA210989NCI NIH HHS U24 CA210990NCI NIH HHS U24 CA210999NCI NIH HHS U24 CA211000NCI NIH HHS U24 CA211006NIEHS NIH HHS P30 ES010126
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.
Indexed as
Adenocarcinoma of LungHumansKelch-Like ECH-Associated Protein 1Lung NeoplasmsTachykininsWhole Genome SequencingKEAP1 protein, humanKelch-Like ECH-Associated Protein 1ranatachykinin ATachykininsdrivergenome analysislung adenocarcinomanoncodingoncogeneprecision oncologystructural variationTCGAtumor suppressorwhole genome sequencing
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