Evidence map›Paper›PMID 41279405›Full record

ArticlebioRxiv : the preprint server for biology2025

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 readPreprint
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In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

19 authors.

Jessica D St LaurentDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA 02215.ORCID 0000-0002-9422-8713
Grace D XuDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA 02215.
Alexander W YingDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA 02215.ORCID 0009-0005-9826-0613
Bengul GokbayrakDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0003-0504-6078
Ajinkya PatilDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA 02215.ORCID 0000-0003-1080-1146
Joao A PauloDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-4291-413X
Kasey S CervantesDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA 02215.
Shary ChenDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
William W FengDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-8976-5020
Akshay SankarDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA 02215.
Daniel D Samé GuerraDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA 02215.
Jun QiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Dana S NeelDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA 02215.ORCID 0000-0002-1788-4784
Jason L HornickDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-6475-8345
David L KolinDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-7631-6525
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-7626-0034
David G HunstmanDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Yemin WangDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0002-2970-9510
Cigall KadochDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA 02215.ORCID 0000-0002-4058-5985

Funding

REPRODUCTIVE SCIENTIST TRAINING PROGRAMK12HD000849 · NICHD · WASHINGTON UNIVERSITY · PI Danny J Schust · 1988 to 2026
$33.2M
NICHD NIH HHS K12 HD000849
6 · The paper itself

Abstract

The mammalian SWI/SNF (mSWI/SNF) family of chromatin remodelers govern cell type-specific chromatin accessibility and gene expression and assemble as three distinct complexes: canonical BAF (cBAF), Polybromo-associated BAF (PBAF), and non-canonical 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/undifferentiated endometrial carcinomas (DDEC/UECs). Here, in cellular models and primary human tumors, we find that ARID1A/B deficiency-mediated cBAF loss results in increased ncBAF and PBAF biochemical abundance and chromatin-level functions to maintain the DDEC oncogenic state. Further, treatment with clinical-grade SMARCA4/2 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/UEC and other cBAF-disrupted cancer types.

Identifiers

PMID41279405
PMCPMC12632890

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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.