Evidence map›Paper›PMID 41116019›Full record

ArticleNature genetics2025

Shifted assembly and function of mSWI/SNF family subcomplexes underlie targetable dependencies in dedifferentiated endometrial carcinomas.

Jessica D St Laurent, Grace D Xu, Alexander W Ying, Bengul Gokbayrak, Ajinkya Patil, Joao A Paulo, Kasey S Cervantes, Shary Chen, William W Feng, Akshay Sankar and 9 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Jessica D St LaurentDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Grace D Xu *Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0009-0005-1894-0089
Alexander W Ying *Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Bengul GokbayrakDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0003-0504-6078
Ajinkya PatilDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Joao A PauloDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4291-413X
Kasey S CervantesDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Shary ChenDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
William W FengDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8976-5020
Akshay SankarDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Daniel D Samé GuerraDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Jun QiDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1461-3356
Dana S NeelDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Jason L HornickDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6475-8345
David L KolinDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7631-6525
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7626-0034
David G HunstmanDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Yemin Wang *Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0002-2970-9510
Cigall KadochDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. Cigall_kadoch@dfci.harvard.edu.ORCID http://orcid.org/0000-0002-4058-5985

Funding

Tri-Institutional PhD Program in Computational Biology & MedicineT32GM132083 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Doron Betel, Iman Hajirasouliha · 2020 to 2026
$3.6M
Howard Hughes Medical Institute (HHMI) InvestigatorNIGMS NIH HHS T32 GM132083Terry Fox Research Institute (Institut de Recherche Terry Fox) 1082Terry Fox Research Institute (Institut de Recherche Terry Fox) 1116U.S. Department of Health & Human Services | National Institutes of Health (NIH) K12-HD000849-37
6 · The paper itself

Abstract

The mammalian (m)SWI/SNF family of chromatin remodelers govern cell type-specific chromatin accessibility and gene expression and assemble as three distinct complexes: canonical BRG1-associated or BRM-associated factor (cBAF), poly(bromo)-associated BAF (PBAF) and noncanonical BAF (ncBAF). ARID1A and ARID1B are paralog subunits that specifically nucleate the assembly of cBAF complexes and are frequently co-mutated in highly aggressive dedifferentiated or undifferentiated endometrial carcinomas (DDEC/UECs). Here in cellular models and primary human tumors, we find that ARID1A and/or ARID1B (ARID1A/B) deficiency-mediated cBAF loss results in increased ncBAF and PBAF biochemical abundance and chromatin-level functions to maintain the DDEC oncogenic state. Furthermore, treatment with clinical-grade SMARCA4 and/or SMARCA2 ATPase inhibitors markedly attenuates DDEC cell proliferation and tumor growth in vivo and synergizes with carboplatin-based chemotherapy to extend survival. These findings reveal the oncogenic contributions of shifted mSWI/SNF family complex stoichiometry and resulting gene-regulatory dysregulation and suggest therapeutic utility of mSWI/SNF small molecule inhibitors in DDEC/UECs and other cBAF-disrupted cancer types.

Indexed as

DNA-Binding ProteinsEndometrial NeoplasmsTranscription FactorsAnimalsATPases Associated with Diverse Cellular ActivitiesCell Line, TumorCell ProliferationChromatin Assembly and DisassemblyChromosomal Proteins, Non-HistoneDNA HelicasesFemaleGene Expression Regulation, NeoplasticHumansMiceNuclear ProteinsARID1A protein, humanARID1B protein, humanATPases Associated with Diverse Cellular ActivitiesChromosomal Proteins, Non-HistoneDNA-Binding ProteinsDNA HelicasesNuclear ProteinsSMARCA2 protein, humanSMARCA4 protein, humanTranscription Factors

Identifiers

PMID41116019

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.