Evidence map›Paper›PMID 39707510›Full record

ArticleGenome biology2024

Multi-omics approaches reveal that diffuse midline gliomas present altered DNA replication and are susceptible to replication stress therapy.

Anastasia E Hains, Kashish Chetal, Tsunetoshi Nakatani, Joana G Marques, Andreas Ettinger, Carlos A O Biagi Junior, Adriana Gonzalez-Sandoval, Renjitha Pillai, Mariella G Filbin, Maria-Elena Torres-Padilla and 2 more

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Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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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.

Anastasia E HainsDepartment of Pathology, Stanford University, Stanford, CA, 94305, USA.
Kashish ChetalDepartment of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Tsunetoshi NakataniInstitute of Epigenetics and Stem Cells, Helmholtz Munich, Munich, Germany.
Joana G MarquesDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA, 02215, USA.
Andreas EttingerInstitute of Epigenetics and Stem Cells, Helmholtz Munich, Munich, Germany.
Carlos A O Biagi JuniorDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA, 02215, USA.
Adriana Gonzalez-SandovalDepartment of Pathology, Stanford University, Stanford, CA, 94305, USA.
Renjitha PillaiDepartment of Pathology, Stanford University, Stanford, CA, 94305, USA.
Mariella G FilbinDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA, 02215, USA.
Maria-Elena Torres-PadillaInstitute of Epigenetics and Stem Cells, Helmholtz Munich, Munich, Germany.
Ruslan I SadreyevDepartment of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Capucine Van RechemDepartment of Pathology, Stanford University, Stanford, CA, 94305, USA. cvrechem@stanford.edu.

Funding

How the 3D Architecture of the Brain Shapes Cancer Cell Fate DecisionsDP2NS127705 · NINDS · DANA-FARBER CANCER INST · PI FILBIN, MARIELLA GRUBER · 2021 to 2024
$2.7M
Four Laser, 18 Color Cell Sorter in the SSFFS10RR025518 · NCRR · STANFORD UNIVERSITY · PI HERZENBERG, LEONARD A · 2009 to 2009
$500k
NCRR NIH HHS S10 RR025518NINDS NIH HHS DP2 NS127705
6 · The paper itself

Abstract

backgroundThe fatal diffuse midline gliomas (DMG) are characterized by an undruggable H3K27M mutation in H3.1 or H3.3. K27M impairs normal development by stalling differentiation. The identification of targetable pathways remains very poorly explored. Toward this goal, we undertake a multi-omics approach to evaluate replication timing profiles, transcriptomics, and cell cycle features in DMG cells from both H3.1K27M and H3.3K27M subgroups and perform a comparative, integrative data analysis with healthy brain tissue.

resultsDMG cells present differential replication timing in each subgroup, which, in turn, correlates with significant differential gene expression. Differentially expressed genes in S phase are involved in various pathways related to DNA replication. We detect increased expression of DNA replication genes earlier in the cell cycle in DMG cell lines compared to normal brain cells. Furthermore, the distance between origins of replication in DMG cells is smaller than in normal brain cells and their fork speed is slower, a read-out of replication stress. Consistent with these findings, DMG tumors present high replication stress signatures in comparison to normal brain cells. Finally, DMG cells are specifically sensitive to replication stress therapy.

conclusionsThis whole genome multi-omics approach provides insights into the cell cycle regulation of DMG via the H3K27M mutations and establishes a pharmacologic vulnerability in DNA replication, which resolves a potentially novel therapeutic strategy for this non-curable disease.

Indexed as

Brain NeoplasmsDNA ReplicationGliomaCell CycleCell Line, TumorGene Expression Regulation, NeoplasticHistonesHumansMultiomicsMutationTranscriptomeHistonesCell cycleDiffuse midline gliomas H3 K27-alteredH3K27MReplication stressReplication timing

Identifiers

PMID39707510
PMCPMC11660928

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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.