Evidence map›Paper›PMID 38992221›Full record

ArticleScientific reports2024

PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression.

Christin Schmidt, Sarah Cohen, Brian L Gudenas, Sarah Husain, Annika Carlson, Samantha Westelman, Linyu Wang, Joanna J Phillips, Paul A Northcott, William A Weiss and 1 more

Abstract read
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Christin SchmidtDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Sarah CohenDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Brian L GudenasDivision of Brain Tumor Research, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Sarah HusainHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Annika CarlsonDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Samantha WestelmanHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Linyu WangHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Joanna J PhillipsDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Paul A NorthcottDivision of Brain Tumor Research, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
William A WeissDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA. william.weiss@ucsf.edu.
Bjoern SchwerDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA. bjoern.schwer@ucsf.edu.

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Kate Taylor Shumate · 1999 to 2026
$209.7M
Mouse models to discover new drivers of medulloblastomaR01CA159859 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael D. Taylor, WILLIAM A WEISS · 2011 to 2026
$10.4M
CCL2 and CCR2 as metastatic drivers and therapeutic targets in medulloblastomaR01CA255369 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GARZIA, LIVIA, TAYLOR, MICHAEL D. · 2021 to 2025
$3.9M
Remodeling the translatome in N-myc mediated medulloblastoma and its therapeutic implicationsR01NS125668 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Davide Ruggero, WILLIAM A WEISS · 2022 to 2026
$3.3M
Prevention and treatment of lethal metastases in group 3 medulloblastomaR01NS106155 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI TAYLOR, MICHAEL D., WEISS, WILLIAM A · 2018 to 2022
$2.8M
Role of DNA double-strand breaks in neural function and homeostasisR01AG064363 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SCHWER, BJOERN · 2020 to 2024
$1.7M
Congressionally Directed Medical Research Programs PRCRP Horizon AwardNCI NIH HHS P30 CA082103NCI NIH HHS R01 CA159859NCI NIH HHS R01 CA255369NIA NIH HHS R01 AG064363NIH HHS R01AG064363NIH HHS R01NS125668NINDS NIH HHS R01 NS106155NINDS NIH HHS R01 NS125668Sidney Kimmel Foundation Kimmel Scholar Award
6 · The paper itself

Abstract

SNCAIP duplication may promote Group 4 medulloblastoma via induction of PRDM6, a poorly characterized member of the PRDF1 and RIZ1 homology domain-containing (PRDM) family of transcription factors. Here, we investigated the function of PRDM6 in human hindbrain neuroepithelial stem cells and tested PRDM6 as a driver of Group 4 medulloblastoma. We report that human PRDM6 localizes predominantly to the nucleus, where it causes widespread repression of chromatin accessibility and complex alterations of gene expression patterns. Genome-wide mapping of PRDM6 binding reveals that PRDM6 binds to chromatin regions marked by histone H3 lysine 27 trimethylation that are located within, or proximal to, genes. Moreover, we show that PRDM6 expression in neuroepithelial stem cells promotes medulloblastoma. Surprisingly, medulloblastomas derived from PRDM6-expressing neuroepithelial stem cells match human Group 3, but not Group 4, medulloblastoma. We conclude that PRDM6 expression has oncogenic potential but is insufficient to drive Group 4 medulloblastoma from neuroepithelial stem cells. We propose that both PRDM6 and additional factors, such as specific cell-of-origin features, are required for Group 4 medulloblastoma. Given the lack of PRDM6 expression in normal tissues and its oncogenic potential shown here, we suggest that PRDM6 inhibition may have therapeutic value in PRDM6-expressing medulloblastomas.

Indexed as

ChromatinMedulloblastomaAnimalsCell Line, TumorCerebellar NeoplasmsGene Expression Regulation, NeoplasticHistone-Lysine N-MethyltransferaseHistonesHumansMuscle ProteinsNeuroepithelial CellsTranscription FactorsChromatinHistone-Lysine N-MethyltransferaseHistonesMuscle ProteinsPRDM6 protein, humanTranscription Factors

Identifiers

PMID38992221
PMCPMC11239875

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.