Evidence map›Paper›PMID 41526710›Full record

ArticleCommunications biology2026

The dynamics of mutational selection in cutaneous squamous carcinogenesis.

Greta Skrupskelyte, Joanna C Fowler, Stefan Dentro, Carine Winkler, Irina Abnizova, Niklas Beumer, Roshan Sood, Thomas Quarrell, Charlotte King, Jivko Kamarashev and 5 more

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In one paragraph

Article in Communications biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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

5 · Who and what money

Authors and funding

15 authors.

Greta SkrupskelyteCambridge Stem cell Institute, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0009-0006-8903-606X
Joanna C FowlerWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.ORCID http://orcid.org/0000-0001-7546-369X
Stefan DentroWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
Carine WinklerCentre for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.ORCID http://orcid.org/0009-0006-9936-0031
Irina AbnizovaWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
Niklas BeumerEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, UK.ORCID http://orcid.org/0000-0001-6538-0217
Roshan SoodWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.ORCID http://orcid.org/0000-0002-1318-7025
Thomas QuarrellSchool of Clinical Medicine, Addenbrooke's Hospital, Hills Rd, Cambridge, UK.
Charlotte KingWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
Jivko KamarashevDepartment of Dermatology, UniversitätsSpital, Zurich, Switzerland.
Emmanuella GuenovaClinical Department of Immunodermatology, Kepler University Clinic and Medical Faculty, Johannes Kepler University, Mainz, Austria.
Moritz GerstungEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, UK.ORCID http://orcid.org/0000-0001-6709-963X
Benjamin A HallDept of Med Physics & Biomedical Engineering, University College London, London, UK.ORCID http://orcid.org/0000-0003-0355-2946
Liliane MichalikCentre for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
Philip H JonesWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. pj3@sanger.ac.uk.ORCID http://orcid.org/0000-0002-5904-795X

Funding

Cancer Research UK (CRUK) C609/A27326Cancer Research UK (CRUK) DRCRPG-Nov24/100003Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 31003A-169232Wellcome TrustWellcome Trust (Wellcome) 220540/Z/20/A
6 · The paper itself

Abstract

Identifying the mutant genes that are selected during carcinogenesis is key to identifying candidates for intervention and understanding the processes that promote transformation. Here we applied two selection metrics to study the dynamics of mutational selection in a mouse model of ultraviolet light driven skin carcinogenesis in which multiple synchronous tumors develop in each animal. Sequencing normal skin and tumors over a time course revealed two genetic routes to squamous carcinoma. Nonsynonymous Trp53 mutants were positively selected in both epidermis and tumors and present in 90% of tumors. The remaining tumors carried other oncogenic mutants, including activating Kras mutations. However, other positively selected mutant genes lost their competitive advantage in heavily mutated epidermis and in tumors. We found ten mutant genes under negative selection in normal skin, one of which was also negatively selected in tumors. In addition one gene was negatively selected in tumors but not normal skin. We conclude that analysing selection in normal tissue alongside tumors may resolve the dynamics of selection in carcinogenesis and refine the identification of cancer drivers.

Indexed as

CarcinogenesisCarcinoma, Squamous CellMutationSelection, GeneticSkin NeoplasmsAnimalsCell Transformation, NeoplasticCutaneous Squamous Cell CarcinomaMiceTumor Suppressor Protein p53Ultraviolet RaysTumor Suppressor Protein p53

Identifiers

PMID41526710
PMCPMC12855962

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Registered trials

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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.