ArticleNature genetics2021
Genomic and evolutionary classification of lung cancer in never smokers.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06473870 (Understanding Lung Cancer Related Risk Factors and Their Impact), which is not on this map. Cited by 154 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
154citing papers in PubMed, 2 pooled it
13.2field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Understanding Lung Cancer Related Risk Factors and Their Impact
Who cites it
154 citing papers in PubMed, 2 syntheses or guidelines pooled it, 226 citations in OpenAlex.
- Adiposity and cancer: systematic review and meta-analysis.Nature metabolism · 2026Pooled it
- Multi-ancestry GWAS meta-analyses of lung cancer reveal susceptibility loci and elucidate smoking-independent genetic risk.Nature communications · 2024Pooled it
- Hallmarks of lung cancer driven by inhalable particulate matter: From cell-intrinsic oncogenic traits to microenvironment remodeling.Innovation (Cambridge (Mass.)) · 2026Review
- Recent advances in engineered nanozymes for precision lung cancer therapy.Materials today. Bio · 2026Review
- Germline determinants of risk and molecular subtype in young-onset lung cancer.medRxiv : the preprint server for health sciences · 2026Article
- Lobar-level radiomic clustering reveals background lung changes associated with lung cancer risk: a new perspective for early screening.Insights into imaging · 2026Article
- Lung Cancer Screening and Prevention: Beyond Conventional Strategies in a Rapidly Changing Global Milieu.American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting · 2026Review
- Somatic copy number variation as a prognostic marker for recurrence in never-smokers with early-stage lung adenocarcinoma.International journal of cancer · 2026Article
- A Roadmap to Transform Lung Cancer Outcomes: Priorities in Biology, Therapeutic Innovation, Early Detection, Prevention, and Interception.Cancer discovery · 2026Review
- Motif-Centered Analyses Reveal Universal and Tissue-Specific Mutagenic Mechanisms Operating in the Human Body.bioRxiv : the preprint server for biology · 2026Article
- Impact of particulate matter 2.5 on a mouse model of lung adenocarcinoma.BMC pulmonary medicine · 2026Article
- VEXAS syndrome.Nature reviews. Disease primers · 2026Review
- Genomic Characterization of Lung Cancer in Never-Smokers Using Deep Learning.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2026Article
- A Prognostic Signature for Lung Adenocarcinoma in Patients Who Have Never Smoked.Cancer discovery · 2026Article
- Rethinking the microenvironment's role in chemical-induced malignancy.Toxicological sciences : an official journal of the Society of Toxicology · 2026Review
- Multiomics assessment of lung adenocarcinoma subtypes defined through tumor purity-adjusted DNA methylation.Genome medicine · 2026Article
- The Landscape of Clinical Trials in Never-Smoker Non-Small-Cell Lung Cancer: Registered Evidence and Persistent Gaps.Cancers · 2026Article
- Article
- Integrative clinico-molecular analysis reveals actionable subtypes and biomarkers in lung adenocarcinoma.Cell discovery · 2026Article
- Review
94 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
61 authors at 19 institutions in 5 countries.
Tongwu ZhangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-2124-2706
Philippe JoubertInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Quebec, Canada.
Naser Ansari-PourBig Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-0908-0484
Wei ZhaoDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-5103-3871
Phuc H HoangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-9265-8525
Rachel LokangaCancer Genomics Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Aaron L MoyeStem Cell Program and Divisions of Hematology/Oncology and Pulmonary Medicine, Boston Children's Hospital, Boston, MA, USA.
Jennifer RosenbaumWestat, Rockville, MD, USA.
Abel Gonzalez-PerezInstitute for Research in Biomedicine Barcelona, The Barcelona Institute of Science and Technology, Barcelona, Spain.ORCID http://orcid.org/0000-0002-8582-4660
Francisco Martínez-JiménezInstitute for Research in Biomedicine Barcelona, The Barcelona Institute of Science and Technology, Barcelona, Spain.ORCID http://orcid.org/0000-0001-7804-1134
Andrea CastroDepartment of Medicine, Division of Medical Genetics, University of California San Diego, San Diego, CA, USA.ORCID http://orcid.org/0000-0002-5873-2496
Lucia Anna MuscarellaLaboratory of Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.ORCID http://orcid.org/0000-0002-1866-8151
Paul HofmanLaboratory of Clinical and Experimental Pathology, University Hospital Federation OncoAge, Nice Hospital, University Côte d'Azur, Nice, France.
Dario ConsonniFondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.ORCID http://orcid.org/0000-0002-8935-3843
Angela C PesatoriFondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.ORCID http://orcid.org/0000-0002-0261-3252
Michael KebedeDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Mengying LiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Bonnie E Gould RothbergSmilow Cancer Hospital, Yale-New Haven Health, New Haven, CT, USA.
Iliana PenevaWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Matthew B SchabathDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.ORCID http://orcid.org/0000-0003-3241-3216
Maria Luana PoetaDepartment of Bioscience, Biotechnology and Biopharmaceutics, University of Bari, Bari, Italy.ORCID http://orcid.org/0000-0002-6364-727X
Manuela CostantiniDepartment of Urology, Istituto di Ricovero e Cura a Carattere Scientifico Regina Elena National Cancer Institute, Rome, Italy.
Daniela HirschCancer Genomics Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-8883-922X
Kerstin Heselmeyer-HaddadCancer Genomics Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Amy HutchinsonDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Mary OlanichDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Scott M LawrenceDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-5297-7978
Petra LenzDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Maire DugganDepartment of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.ORCID http://orcid.org/0000-0001-6625-7683
Praphulla M S BhawsarDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Jian SangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Jung KimDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-6274-2841
Laura MendozaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-4866-6357
Natalie SainiGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle, NC, USA.
Leszek J KlimczakIntegrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, Research Triangle, NC, USA.ORCID http://orcid.org/0000-0003-3048-2576
S M Ashiqul IslamDepartment of Cellular and Molecular Medicine and Department of Bioengineering and Moores Cancer Center, University of California San Diego, San Diego, CA, USA.
Burcak OtluDepartment of Cellular and Molecular Medicine and Department of Bioengineering and Moores Cancer Center, University of California San Diego, San Diego, CA, USA.ORCID http://orcid.org/0000-0002-4931-7979
Azhar KhandekarDepartment of Cellular and Molecular Medicine and Department of Bioengineering and Moores Cancer Center, University of California San Diego, San Diego, CA, USA.
Nathan ColeDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Douglas R StewartDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-8193-1488
Jiyeon ChoiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-0955-2384
Kevin M BrownDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-8558-6711
Neil E CaporasoDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Samuel H WilsonGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle, NC, USA.
Yves PommierDevelopmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Qing LanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Nathaniel RothmanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Jonas S AlmeidaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Hannah CarterDepartment of Medicine, Division of Medical Genetics, University of California San Diego, San Diego, CA, USA.
Thomas RiedCancer Genomics Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Carla F KimStem Cell Program and Divisions of Hematology/Oncology and Pulmonary Medicine, Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2366-9538
Nuria Lopez-BigasInstitute for Research in Biomedicine Barcelona, The Barcelona Institute of Science and Technology, Barcelona, Spain.ORCID http://orcid.org/0000-0003-4925-8988
Montserrat Garcia-ClosasDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-1033-2650
Jianxin ShiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Yohan BosséInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Quebec, Canada.
Bin ZhuDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-0172-5516
Dmitry A GordeninGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle, NC, USA.ORCID http://orcid.org/0000-0002-8399-1836
Ludmil B AlexandrovDepartment of Cellular and Molecular Medicine and Department of Bioengineering and Moores Cancer Center, University of California San Diego, San Diego, CA, USA.ORCID http://orcid.org/0000-0003-3596-4515
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-2324-3393
David C WedgeBig Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-7572-3196
Maria Teresa LandiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. landim@mail.nih.gov.ORCID http://orcid.org/0000-0003-4507-329X
National Cancer Institute · USFrederick National Laboratory for Cancer Research · USTriangle · USUniversity of California San Diego · USBoston Children's Hospital · USInstitute for Research in Biomedicine · ESInstitut universitaire de cardiologie et de pneumologie de Québec · CAOpen Data Institute · GBUniversity of California San Diego Medical Center · USCasa Sollievo della Sofferenza · ITCentre for Human Genetics · GBFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico · ITInstitució Catalana de Recerca i Estudis Avançats · ESMoffitt Cancer Center · USUniversity of Bari Aldo Moro · ITUniversity of Calgary · CAUniversity of Milan · ITWestat (United States) · USYale Cancer Center · US
Funding
WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6MTRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI John L. Cleveland · 1998 to 2026
$93.5MYale SPORE in Lung Cancer (YSILC): The Biology and Personalized Treatment of Lung CancerP50CA196530 · NCI · YALE UNIVERSITY · PI Harriet M. Kluger · 2015 to 2026
$31.1MStudies of Genetic and Environmental EpidemiologyZIACP101231 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI LANDI, MARIA · 2018 to 2025
$23.6MGenome-wide hypermutation and structural instabilityZIAES103266 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI GORDENIN, DMITRY · 2015 to 2025
$18.0MCell-cell interactions governing lung epithelial progenitor cellsR35HL150876 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI Carla F. Kim · 2020 to 2026
$6.2MBIOLOGY OF MAMMALIAN BASE EXCISION REPAIRZ01ES050159 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WILSON, SAMUEL H · 1997 to 2008
$4.5MDetecting Mutational Signatures of Environmental Mutagens in Heathy Individuals for Personalized Cancer PreventionR01ES032547 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ALEXANDROV, LUDMIL B · 2021 to 2025
$3.4MPrognostic markers in metastatic melanomaK08CA151645 · NCI · YALE UNIVERSITY · PI GOULD ROTHBERG, BONNIE ELYSSA · 2010 to 2014
$527kIntramural NIH HHS Z01 ES050159Intramural NIH HHS Z99 CA999999Intramural NIH HHS ZIA CP101231Intramural NIH HHS ZIA ES103266NCI NIH HHS 75N91019D00024NCI NIH HHS HHSN261201800001CNCI NIH HHS K08 CA151645NCI NIH HHS P30 CA076292NCI NIH HHS P50 CA196530NHLBI NIH HHS R35 HL150876NIEHS NIH HHS R01 ES032547Wellcome TrustWellcome Trust 203141/Z/16/Z
Abstract
Lung cancer in never smokers (LCINS) is a common cause of cancer mortality but its genomic landscape is poorly characterized. Here high-coverage whole-genome sequencing of 232 LCINS showed 3 subtypes defined by copy number aberrations. The dominant subtype (piano), which is rare in lung cancer in smokers, features somatic UBA1 mutations, germline AR variants and stem cell-like properties, including low mutational burden, high intratumor heterogeneity, long telomeres, frequent KRAS mutations and slow growth, as suggested by the occurrence of cancer drivers' progenitor cells many years before tumor diagnosis. The other subtypes are characterized by specific amplifications and EGFR mutations (mezzo-forte) and whole-genome doubling (forte). No strong tobacco smoking signatures were detected, even in cases with exposure to secondhand tobacco smoke. Genes within the receptor tyrosine kinase-Ras pathway had distinct impacts on survival; five genomic alterations independently doubled mortality. These findings create avenues for personalized treatment in LCINS.
Indexed as
AdultAgedAged, 80 and overDNA Copy Number VariationsErbB ReceptorsFemaleGenomeGenome-Wide Association StudyHumansLung NeoplasmsMaleMiddle AgedNeoplastic Stem CellsNon-SmokersProto-Oncogene Proteins p21(ras)Receptors, AndrogenAR protein, humanEGFR protein, humanErbB ReceptorsKRAS protein, humanProto-Oncogene Proteins p21(ras)Receptors, AndrogenUBA1 protein, humanUbiquitin-Activating Enzymes
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Registered trials
NCT06473870ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.