Evidence map›Paper›PMID 41991531›Full record

ArticleNature communications2026

Clonal biases dictate availability of colonic cancer driver mutations for transformation.

Nefeli Skoufou-Papoutsaki, Richard Kemp, Sam Adler, Kate Marks, Anne-Claire Girard, Shenay Mehmed, Filipe C Lourenço, Elisa B Moutin, Rogier Ten Hoopen, Edward Morrissey and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

12 authors.

Nefeli Skoufou-PapoutsakiCRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
Richard KempCRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
Sam AdlerCRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
Kate MarksPathology and Data Analytics, Leeds Institute of Medical Research, University of Leeds School of Medicine, University of Leeds, Leeds, UK.
Anne-Claire GirardCRUK Cambridge Institute, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0009-0009-1331-6411
Shenay MehmedCRUK Cambridge Institute, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0009-0006-2178-618X
Filipe C LourençoCRUK Cambridge Institute, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-9655-2488
Elisa B MoutinCRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
Rogier Ten HoopenDepartment of Oncology, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-0655-9182
Edward MorrisseyMRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Douglas J WintonCRUK Cambridge Institute, University of Cambridge, Cambridge, UK. Doug.Winton@cruk.cam.ac.uk.ORCID http://orcid.org/0000-0001-6067-7927
David S TourignySchool of Mathematics, University of Birmingham, Birmingham, UK. d.tourigny@bham.ac.uk.ORCID http://orcid.org/0000-0002-3987-8078

Funding

Cancer Research UK (CRUK) A24456Wellcome Trust 103805Wellcome Trust (Wellcome) 102160/Z/13/Z
6 · The paper itself

Abstract

Aged normal tissues harbour cancer mutations predisposing to transformation. However, how different pro-oncogenic events in the human colon compare in frequency, behaviour and subsequent transformation risk remains unclear. Here, we analyse mutation hotspot regions in five colorectal cancer genes (APC, KRAS, TP53, FBXW7 and CTNNB1) using targeted sequencing of 76,800 normal colonic glands from 56 patients. We show that cancer-driving mutations are present in all genes in histologically normal tissue. Reconstruction of clone dynamics reveals that FBXW7 R465C mutations preferentially become fixed within the tissue, whereas KRAS G12 mutations strongly promote expansion. Modelling mutation order indicates that early loss of both APC copies increasingly favours an APC-first pathway with age, while KRAS activation is equally likely to initiate events in younger individuals. Spatial transcriptomics highlights phenotypic heterogeneity among KRAS mutant clones, with mixed lineage presentation observed only in a subset, a state linked to elevated transformation risk in other organs.

Indexed as

Cell Transformation, NeoplasticColonic NeoplasmsMutationAdenomatous Polyposis Coli Proteinbeta CateninColonF-Box-WD Repeat-Containing Protein 7HumansProto-Oncogene Proteins p21(ras)Tumor Suppressor Protein p53Adenomatous Polyposis Coli ProteinAPC protein, humanbeta CateninCTNNB1 protein, humanF-Box-WD Repeat-Containing Protein 7FBXW7 protein, humanKRAS protein, humanProto-Oncogene Proteins p21(ras)TP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID41991531
PMCPMC13269798

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.