Evidence map›Paper›PMID 40034649›Full record

ArticlebioRxiv : the preprint server for biology2024

Three-dimensional regulatory hubs support oncogenic programs in glioblastoma.

Sarah L Breves, Dafne Campigli Di Giammartino, James Nicholson, Stefano Cirigliano, Syed Raza Mahmood, Uk Jin Lee, Alexander Martinez-Fundichely, Johannes Jungverdorben, Richa Singhania, Sandy Rajkumar and 6 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. 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

5 · Who and what money

Authors and funding

16 authors.

Sarah L BrevesSanford I. Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, United States.ORCID 0000-0003-1182-8906
Dafne Campigli Di GiammartinoSanford I. Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, United States.
James NicholsonMeyer Cancer Center, Division of Neuro-Oncology, Department of Neurology, Sandra and Edward Meyer Cancer Center, New York-Presbyterian Hospital/Weill Cornell Medicine, New York, NY, USA.
Stefano CiriglianoMeyer Cancer Center, Division of Neuro-Oncology, Department of Neurology, Sandra and Edward Meyer Cancer Center, New York-Presbyterian Hospital/Weill Cornell Medicine, New York, NY, USA.
Syed Raza MahmoodSanford I. Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, United States.
Uk Jin LeeSanford I. Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, United States.
Alexander Martinez-FundichelyInstitute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, 10021, USA.
Johannes JungverdorbenThe Center for Stem Cell Biology, Developmental Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY, USA.
Richa SinghaniaMeyer Cancer Center, Division of Neuro-Oncology, Department of Neurology, Sandra and Edward Meyer Cancer Center, New York-Presbyterian Hospital/Weill Cornell Medicine, New York, NY, USA.
Sandy RajkumarSanford I. Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, United States.
Raphael KirouSanford I. Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, United States.
Lorenz StuderThe Center for Stem Cell Biology, Developmental Biology Program, Sloan Kettering Institute for Cancer Research, New York, NY, USA.
Ekta KhuranaInstitute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, 10021, USA.
Alexander PolyzosSanford I. Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, United States.
Howard A Fine3D Chromatin Conformation and RNA genomics laboratory, Istituto Italiano di Tecnologia (IIT), Center for Human Technologies (CHT), Genova, Italy (current affiliation).
Effie ApostolouSanford I. Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, United States.

Funding

Training Program in Developmental BiologyT32HD060600 · NICHD · WEILL MEDICAL COLL OF CORNELL UNIV · PI BAO, ZHIRONG, STUHLMANN, HEIDI · 2010 to 2024
$3.5M
Identifying and Targeting 3D Regulatory Nodes that Maintain Glioblastoma Programs.R01NS136475 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Effie Apostolou, Howard A. Fine · 2024 to 2026
$2.0M
NICHD NIH HHS T32 HD060600NINDS NIH HHS R01 NS136475
6 · The paper itself

Abstract

Dysregulation of enhancer-promoter communication in the context of the three-dimensional (3D) nucleus is increasingly recognized as a potential driver of oncogenic programs. Here, we profiled the 3D enhancer-promoter networks of primary patient-derived glioblastoma stem cells (GSCs) in comparison with neuronal stem cells (NSCs) to identify potential central nodes and vulnerabilities in the regulatory logic of this devastating cancer. Specifically, we focused on hyperconnected 3D regulatory hubs and demonstrated that hub-interacting genes exhibit high and coordinated expression at the single-cell level and strong association with oncogenic programs that distinguish IDH-wt glioblastoma patients from low-grade glioma. Epigenetic silencing of a recurrent 3D enhancer hub-with an uncharacterized role in glioblastoma-was sufficient to cause concordant downregulation of multiple hub-connected genes along with significant shifts in transcriptional states and reduced clonogenicity. By integrating published datasets from other cancer types, we also identified both universal and cancer type-specific 3D regulatory hubs which enrich for varying oncogenic programs and nominate specific factors associated with worse outcomes. Genetic alterations, such as focal duplications, could explain only a small fraction of the detected hyperconnected hubs and their increased activity. Overall, our study provides computational and experimental support for the potential central role of 3D regulatory hubs in controlling oncogenic programs and properties.

Indexed as

3D chromatin organizationclonogenicityCRISPRienhancer hubsenhancer-promoter interactionsglioblastomaHiChIPoncogenic programsingle-cell RNA-seqstructural variants

Identifiers

PMID40034649
PMCPMC11875237

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.