Evidence map›Paper›PMID 42332268›Full record

ArticleNature genetics2026

Longitudinal changes in DNA methylation in IDH-mutant glioma fuel disease progression through altered cell state differentiation.

Masashi Nomura, Ramya Raviram, Joshua S Schiffman, Lillian Bussema, Vivian Lu, Noelle Wheeler, John J Y Lee, Yilin Fan, Mian Hua Zheng, Florian Ruiz and 12 more

Abstract read
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. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. 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

22 authors.

Masashi Nomura *Department of Pathology and Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6095-7849
Ramya Raviram *New York Genome Center, New York, NY, USA.
Joshua S Schiffman *New York Genome Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-1028-1438
Lillian BussemaDepartment of Pathology and Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-5469-3816
Vivian LuNew York Genome Center, New York, NY, USA.
Noelle WheelerNew York Genome Center, New York, NY, USA.
John J Y LeeDepartment of Pathology and Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Yilin FanDepartment of Pathology and Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Mian Hua ZhengNew York Genome Center, New York, NY, USA.
Florian RuizDepartment of Pathology and Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Husain DanishNew York Genome Center, New York, NY, USA.
Sorcha KellettDivision of Neurosurgery, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Labeeba NusratDivision of Neurosurgery, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Ronan ChaligneComputational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-4332-3291
Jason T HuseDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-4514-0640
W K Alfred YungDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-1669-0793
Shota TanakaDepartment of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Nobuhito SaitoDepartment of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Sunit DasDivision of Neurosurgery, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Catherine PotenskiNew York Genome Center, New York, NY, USA.
Dan A LandauNew York Genome Center, New York, NY, USA. dal3005@med.cornell.edu.ORCID http://orcid.org/0000-0003-2346-9541
Mario L SuvàDepartment of Pathology and Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Suva.Mario@mgh.harvard.edu.ORCID http://orcid.org/0000-0001-9898-5351

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Center for Integrated Cellular Analysis - Valeria A. Sanchez EstradaRM1HG011014 · NHGRI · NEW YORK GENOME CENTER · PI LANDAU, DAN, SATIJA, RAHUL · 2020 to 2025
$22.1M
Dissecting the cellular hierarchies of malignant gliomas by single-cell functional genomicsR37CA245523 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Mario Luca Suva · 2020 to 2026
$2.8M
Deciphering heritability, plasticity and differentiation trajectories in gliomas via single-cell multi-omicsR01CA258763 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI SUVA, MARIO LUCA · 2021 to 2025
$2.8M
Dissecting the Determinants of IDH-mutant Gliomas Response to Mutant IDH InhibitorsR01CA276765 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel P. Cahill, Mario Luca Suva · 2023 to 2026
$2.7M
NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA258763NCI NIH HHS R01 CA276765NCI NIH HHS R37 CA245523NHGRI NIH HHS RM1 HG011014U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA258763U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA276765U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R37CA245523U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) RM1HG011014
6 · The paper itself

Abstract

The progression of isocitrate dehydrogenase-mutant glioma (IDH-G) from slow-growing tumor to fatal disease is associated with transcriptional and DNA methylation changes that remain poorly understood. Here, we profiled a longitudinal cohort of 36 IDH-G samples from 19 patients by joint-capture multi-omic single-nucleus DNA methylation, single-nucleus RNA sequencing and bulk exome sequencing. We show that IDH-G progression is associated with an increase in malignant stem-like states, decreased differentiation and methylation loss, which marks tumors with worse clinical outcome. Methylation loss was uniformly observed across malignant cells within individual tumors, suggesting that it may underlie rather than result from the increase in stem-like states. Analysis of cell-state heritability and plasticity using high-resolution phylogenetic trees links DNA methylation loss to alterations in glioma cell-state encoding and heritability. Our study offers insights into how DNA methylation loss reshapes cellular transitions and how it may mark clinically more aggressive tumors across IDH-G subsets.

Indexed as

Brain NeoplasmsCell DifferentiationDNA MethylationGliomaIsocitrate DehydrogenaseMutationDisease ProgressionExome SequencingGene Expression Regulation, NeoplasticHumansLongitudinal StudiesNeoplastic Stem CellsIsocitrate Dehydrogenase

Identifiers

PMID42332268
PMCPMC13364636

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.