Evidence map›Paper›PMID 42427883›Full record

ArticleResearch square2026

Context-dependent selection sculpts mutational landscapes in the normal lung.

Edward J Evans, Ferriol Calvet, Fabio Marongiu, Faiz Jabbar, Elan Z Eisenmesser, William Hill, Clare Weeden, Oriol Pich, Moumita Ghosh, Robert L Keith and 19 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors.

Edward J EvansDepartments of Biochemistry and Molecular Genetics, Immunology and Microbiology, and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Ferriol CalvetInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain.ORCID 0000-0003-1841-9881
Fabio MarongiuDepartments of Biochemistry and Molecular Genetics, Immunology and Microbiology, and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Faiz JabbarCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Elan Z EisenmesserDepartments of Biochemistry and Molecular Genetics, Immunology and Microbiology, and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
William HillCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Clare WeedenCancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London, UK.
Oriol PichCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.ORCID 0000-0002-1956-1882
Moumita GhoshDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine / Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Robert L KeithDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine / Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
York E MillerDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine / Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Daniel T MerrickDepartment of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Clara I TroccoliDepartments of Biochemistry and Molecular Genetics, Immunology and Microbiology, and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Andrew RowanCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Takahiro KarasakiCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Selvaraju VeeriahCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
David A MooreCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.ORCID 0000-0002-6296-1312
Mihaela AngelovaCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.ORCID 0000-0002-0495-9695
Olivia LucasCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Charlotte GriecoCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.ORCID 0000-0003-3177-7245
Lydia Y LiuCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Cristina Naceur-LombardelliCancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London, UK.ORCID 0000-0002-7097-0307
TRACERx Consortium
PEACE Consortium
Mariam Jamal-HanjaniCancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London, UK.ORCID 0000-0003-1212-1259
Nuria Lopez-BigasInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain.
Emilia L LimCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Charles SwantonCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.ORCID 0000-0002-4299-3018
James DeGregoriDepartments of Biochemistry and Molecular Genetics, Immunology and Microbiology, and Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID 0000-0002-1287-1976

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Training in Translational Research of Lung, Head and Neck CancerT32CA174648 · NCI · UNIVERSITY OF COLORADO DENVER · PI KARAM, SANA D · 2013 to 2022
$4.2M
Training Program in Cancer BiologyT32CA190216 · NCI · UNIVERSITY OF COLORADO DENVER · PI Craig T. Jordan · 2016 to 2026
$3.5M
(PQ1) Progenitor cell malfunction, mutations and changes in microenvironment: A dynamic risk spectrum for cancer evolutionR01CA219893 · NCI · UNIVERSITY OF COLORADO DENVER · PI GHOSH, MOUMITA, MILLER, YORK E · 2017 to 2022
$2.3M
PROMINENT - IRBOT2CA278668 · NCI · FUNDACIO INSTITUT DE RECERCA BIOMEDICA · PI LOPEZ-BIGAS, NURIA · 2022 to 2024
$1.0M
The Molecular Basis of Staphylococcus aureus SplB manipulation of the hostR01AI189606 · NIAID · UNIVERSITY OF COLORADO DENVER · PI ELAN Z EISENMESSER · 2025 to 2026
$780k
Streptococcus pneumoniae HtrA and its target interactionsR21AI190731 · NIAID · UNIVERSITY OF COLORADO DENVER · PI ELAN Z EISENMESSER · 2025 to 2026
$423k
BLRD VA I01 BX004495NCI NIH HHS OT2 CA278668NCI NIH HHS P30 CA046934NCI NIH HHS R01 CA219893NCI NIH HHS T32 CA174648NCI NIH HHS T32 CA190216NIAID NIH HHS R01 AI189606NIAID NIH HHS R21 AI190731Wellcome Trust CC2041
6 · The paper itself

Abstract

Just as organismal evolution is driven by environmental changes, somatic evolution is similarly driven by changes in tissue environments, whether caused by the normal process of aging, by lifestyle choices, or by extrinsic exposures. We present deep mutational profiling using duplex sequencing of over 390 samples of non-malignant lung tissue from 202 subjects, showing how aging, smoking and different anti-cancer therapies are associated with selection for particular mutations in normal lung tissue. Mutations within known cancer driver genes exhibit selection in the normal tissue that differs from that for lung cancers, with a substantially expanded spectrum of sites under selection. Multiregional profiling of mutational landscapes reveals convergent evolution within each individual's lung. Understanding the forces controlling clonal selection as we age and due to lifetime exposures could be critical for controlling multiple diseases of old age.

Identifiers

PMID42427883
PMCPMC13345542

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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.