Evidence map›Paper›PMID 39641785›Full record

ArticleVirchows Archiv : an international journal of pathology2025

YAP1::KMT2A-rearranged sarcomas harbor a unique methylation profile and are distinct from sclerosing epithelioid fibrosarcoma and low-grade fibromyxoid sarcoma.

Laura M Warmke, Baptiste Ameline, Karen J Fritchie, Carina A Dehner, Abbas Agaimy, Nasir Ud Din, Markku M Miettinen, Josephine K Dermawan, John M Gross, Judith J Thangaiah and 10 more

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In one paragraph

Article in Virchows Archiv : an international journal of pathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Transcriptomic Subgroups in Soft Tissue Tumors Correlate with Morphologic Subtype, Genomic Features, and Outcome.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  3. Review
  4. Article
  5. Article
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4 · The record

Corrections and comments

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

20 authors.

Laura M Warmke *Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 W. 11thStreet, Room 4086, Indianapolis, IN, 46202, USA. Laura.Warmke@gmail.com.ORCID http://orcid.org/0000-0002-2989-3282
Baptiste Ameline *Bone Tumor Reference Center at the Institute of Pathology, University Hospital Basel and University of Basel, Basel, Switzerland.
Karen J Fritchie *Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
Carina A DehnerDepartment of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 W. 11thStreet, Room 4086, Indianapolis, IN, 46202, USA.
Abbas AgaimyPathologisches Institut, Universitätsklinikum Erlangen, Erlangen, Germany.
Nasir Ud DinDepartment of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan.
Markku M MiettinenLaboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD, USA.
Josephine K DermawanDepartment of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
John M GrossDepartment of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.
Judith J ThangaiahDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
John S A ChrisingerDepartment of Pathology and Immunology, Washington University, St. Louis, MO, USA.
David I SusterDepartment of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA.
Raul PerretDepartment of Pathology, Institut Bergonié, Bordeaux, France.
François Le LoarerDepartment of Pathology, Institut Bergonié, Bordeaux, France.
Gregory W CharvilleDepartment of Pathology, Stanford University School of Medicine, Palo Alto, CA, USA.
Darya BuehlerDepartment of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Maximus C F YeungThe University of Hong Kong, Queen Mary Hospital, Pok Fu Lam, Hong Kong.
Benjamin F SmithDepartment of Pathology and Laboratory Medicine, Oregon Health & Science University School of Medicine, Portland, OR, USA.
Daniel Baumhoer *Bone Tumor Reference Center at the Institute of Pathology, University Hospital Basel and University of Basel, Basel, Switzerland.
Jessica L Davis *Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 W. 11thStreet, Room 4086, Indianapolis, IN, 46202, USA.

Funding

Immunohistochemical and genomic analysis of tumorsZIABC011427 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MIETTINEN, MARKKU · 2012 to 2025
$24.0M
Intramural NIH HHS ZIA BC011427Universitätsspital Basel Basel Bone Tumor Reference Centre
6 · The paper itself

Abstract

Sclerosing epithelioid fibrosarcoma (SEF) was originally described as a peculiar variant of fibrosarcoma in 1995. Subsequent studies showed that conventional SEF was associated with both immunohistochemical expression of MUC4 and EWSR1/FUS gene rearrangements with CREB3L1 as the predominant fusion partner. Since then, a distinct group of fibrous tumors characterized by YAP1::KMT2A and KMT2A::YAP1 gene rearrangements and SEF-like morphology has been described. These YAP1::KMT2A-rearranged sarcomas were further shown to lack both immunohistochemical expression of MUC4 and canonical EWSR1/FUS gene rearrangements. To better understand whether the YAP1::KMT2A-rearranged sarcomas represent a subset of MUC4-negative SEF or a distinct entity, we studied 22 cases of YAP1::KMT2A-rearranged sarcomas, the largest series to date, and performed a literature review of all previously reported next-generation sequencing (NGS)-confirmed cases. These sarcomas often arose in young adults with a median age of 38 years and a male to female (M:F) ratio of 1.4:1. They predominantly involved somatic soft tissue; however, we report the first case of a tumor that primarily developed inside bone. Immunohistochemical studies showed that the tumors often demonstrated expression of YAP1 and EMA, while all tested cases were negative for MUC4. NGS confirmed the presence of YAP1::KMT2A gene fusions in all cases, some of which initially had false negative results with targeted FISH and solid tumor panel testing. Clinical follow-up information was available in 14 patients with a median follow-up of 25 months (range 1 to 170 months). Local recurrence occurred in three patients (21%) and metastasis developed in seven patients (50%). DNA methylation analysis further showed that YAP1::KMT2A-rearranged sarcomas formed a distinct cluster, which was clearly separate from both conventional SEF and low-grade fibromyxoid sarcoma (LGFMS). These results suggest that YAP1::KMT2A-rearranged sarcomas likely represent a unique sarcoma subtype with propensity for aggressive behavior.

Indexed as

Adaptor Proteins, Signal TransducingBiomarkers, TumorDNA MethylationFibrosarcomaGene RearrangementHistone-Lysine N-MethyltransferaseMyeloid-Lymphoid Leukemia ProteinSarcomaSoft Tissue NeoplasmsTranscription FactorsAdolescentAdultAgedFemaleHumansMaleAdaptor Proteins, Signal TransducingBiomarkers, TumorHistone-Lysine N-MethyltransferaseKMT2A protein, humanMyeloid-Lymphoid Leukemia ProteinTranscription FactorsYAP1 protein, humanYAP-Signaling ProteinsKMT2AMethylationMUC4SarcomaSclerosing epithelioid fibrosarcomaYAP1

Identifiers

PMID39641785
PMCPMC13528201

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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.