Evidence map›Paper›PMID 41040346›Full record

ArticlebioRxiv : the preprint server for biology2025

Intermediately Methylated Regions in Normal Cells Are Epimutation Hotspots in Cancer.

Mohamed Mahgoub, Haley Abel, Nidhi Davarapalli, Heidi Struthers, Emilee Kotnik, Brittany Johnson, Christopher Markovic, Catrina Fronick, Robert Fulton, Michael P Meers and 1 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

11 authors.

Mohamed MahgoubDepartment of Medicine, Division of Oncology, Washington University School of Medicine; St. Louis, MO USA.
Haley AbelDepartment of Medicine, Division of Oncology, Washington University School of Medicine; St. Louis, MO USA.
Nidhi DavarapalliDepartment of Medicine, Division of Oncology, Washington University School of Medicine; St. Louis, MO USA.
Heidi StruthersDepartment of Medicine, Division of Oncology, Washington University School of Medicine; St. Louis, MO USA.
Emilee KotnikDepartment of Medicine, Division of Oncology, Washington University School of Medicine; St. Louis, MO USA.
Brittany JohnsonDepartment of Medicine, Division of Oncology, Washington University School of Medicine; St. Louis, MO USA.
Christopher MarkovicMcDonnell Genome Institute, Washington University School of Medicine; St. Louis, MO USA.
Catrina FronickMcDonnell Genome Institute, Washington University School of Medicine; St. Louis, MO USA.
Robert FultonMcDonnell Genome Institute, Washington University School of Medicine; St. Louis, MO USA.
Michael P MeersDepartment of Genetics, Washington University School of Medicine; St. Louis, MO USA.ORCID 0000-0003-3438-3938
David H SpencerDepartment of Medicine, Division of Oncology, Washington University School of Medicine; St. Louis, MO USA.ORCID 0000-0002-5314-3043

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
Targeting the Bone Marrow Microenvironment In Acute Lymphocytic LeukemiaP50CA171963 · NCI · WASHINGTON UNIVERSITY · PI Daniel C Link · 2013 to 2026
$31.6M
Stem Cell and Transplantation BiologyU54DK106829 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI DEREK L STIREWALT · 2015 to 2026
$9.1M
Dysregulated genome architecture in acute myeloid leukemiaR37CA259359 · NCI · WASHINGTON UNIVERSITY · PI David H Spencer · 2022 to 2026
$1.8M
Molecular impediments to fate-specifying pioneer factor activity during developmentR00GM140251 · NIGMS · WASHINGTON UNIVERSITY · PI MEERS, MICHAEL P · 2023 to 2025
$745k
NCI NIH HHS P30 CA091842NCI NIH HHS P50 CA171963NCI NIH HHS R37 CA259359NIDDK NIH HHS U54 DK106829NIGMS NIH HHS R00 GM140251
6 · The paper itself

Abstract

DNA methylation is altered in all cancers, but the mechanisms responsible for these changes are not well understood. Using data from 100 primary samples, we show that regions with intermediate methylation in normal hematopoietic cells are hotspots for stable, clonal epimutations in acute myeloid leukemia. Analysis of hematopoietic stem cell clones demonstrated that intermediate methylation at epimutation hotspots reflects random allele-specific methylation and expression at the single cell level, representing a previously unrecognized form of somatically acquired imprinting. We identified somatically imprinted regions in other tissues and show they are epimutation hotspots in other cancer types. This demonstrates that random allele-specific methylation is both a general property of normal cells, and a vulnerability that renders them susceptible to cooperating events and clonal selection during cancer.

Identifiers

PMID41040346
PMCPMC12485763

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.