Evidence map›Paper›PMID 42728384›Full record

ArticleNature genetics2026

Cancer treatment alters mutant selection in normal esophagus.

Joanna C Fowler, Giuseppina Arbore, Roshan K Sood, Irina Abnizova, Luca Albarello, Oliver Pickering, Kasumi Murai, Ujjwal Banerjee, Salomé Brunon, Swee Hoe Ong and 12 more

Abstract read
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In one paragraph

Article in Nature genetics, 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

22 authors.

Joanna C FowlerWellcome Sanger Institute, Hinxton, UK.ORCID http://orcid.org/0000-0001-7546-369X
Giuseppina ArboreExperimental Immunology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Roshan K SoodWellcome Sanger Institute, Hinxton, UK.ORCID http://orcid.org/0000-0002-1318-7025
Irina AbnizovaWellcome Sanger Institute, Hinxton, UK.
Luca AlbarelloDepartment of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy.ORCID http://orcid.org/0000-0003-4846-5096
Oliver PickeringSchool of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Kasumi MuraiWellcome Sanger Institute, Hinxton, UK.
Ujjwal BanerjeeWellcome Sanger Institute, Hinxton, UK.
Salomé BrunonWellcome Sanger Institute, Hinxton, UK.
Swee Hoe OngWellcome Sanger Institute, Hinxton, UK.ORCID http://orcid.org/0000-0002-3629-5387
Andrea CossuDepartment of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Ugo ElmoreVita-Salute San Raffaele University, Milan, Italy.
Francesco PuccettiVita-Salute San Raffaele University, Milan, Italy.ORCID http://orcid.org/0000-0001-6638-6880
David Fernandez-AntoranThe Gurdon Institute, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-1608-570X
Giovanni TononVita-Salute San Raffaele University, Milan, Italy.ORCID http://orcid.org/0000-0003-2973-5038
Paolo DellabonaExperimental Immunology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Riccardo RosatiVita-Salute San Raffaele University, Milan, Italy.
Samuel Luke HillSchool of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.ORCID http://orcid.org/0000-0002-9590-2116
Tim UnderwoodSchool of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.ORCID http://orcid.org/0000-0001-9455-2188
Benjamin A HallDepartment of Medical Physics and Biomedical Engineering, University College London, London, UK. b.hall@ucl.ac.uk.ORCID http://orcid.org/0000-0003-0355-2946
David ShorthouseSchool of Pharmacy, University College London, London, UK. d.shorthouse@ucl.ac.uk.ORCID http://orcid.org/0000-0002-3207-3584
Philip H JonesWellcome Sanger Institute, Hinxton, UK. pj3@sanger.ac.uk.ORCID http://orcid.org/0000-0002-5904-795X

Funding

Cancer Research UK (CRUK) A23924Cancer Research UK (CRUK) C609/A27326Cancer Research UK (CRUK) DRCRPG-Nov24/100003Royal Society UF130039Wellcome Trust (Wellcome) 108413/A/15/D
6 · The paper itself

Abstract

Aging epithelial tissues, including the esophagus, are colonized by somatic mutant clones under strong competitive selection. The effect of cancer treatment on mutant selection in normal epithelium is unknown. We hypothesized that some mutant clones may be selectively expanded during treatment. To test this, we sequenced normal esophageal epithelium removed from 70 patients after therapy for esophageal cancer. Patients received either no treatment, combination chemotherapy (FLOT, ECX or EOX) or chemotherapy and radiation therapy (CROSS). Mutant TP53 and PPM1D clones were expanded in patients undergoing CROSS. In the group undergoing FLOT, there was increased selection for RAC1, NFE2L2 and MTOR mutations consistent with these mutants conferring 5-fluorouracil resilience in normal epithelium. Sequencing normal epithelia reveals treatment-specific selection of mutations and may identify genes implicated in cellular responses to therapy.

Indexed as

Esophageal NeoplasmsEsophagusMutationSelection, GeneticFluorouracilHumansrac1 GTP-Binding ProteinTOR Serine-Threonine KinasesTumor Suppressor Protein p53FluorouracilMTOR protein, humanrac1 GTP-Binding ProteinRAC1 protein, humanTOR Serine-Threonine KinasesTumor Suppressor Protein p53

Identifiers

PMID42728384

What OpenQuestion holds

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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.