A novel murine model for sporadic, malignant peripheral nerve sheath tumors, driven by BrafV600E and Pten loss.

Julien Debbache, Myriam Gwerder, Elisabeth Rushing, Lukas Sommer

Abstract read

In one paragraph

Article in Disease models & mechanisms, 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

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

4 authors.

Julien DebbacheUniversity of Zurich, Institute of Anatomy, Winterthurerstrasse 190, 8057 Zürich, Switzerland.ORCID 0000-0002-7308-9777

Myriam GwerderUniversity of Zurich, Institute of Anatomy, Winterthurerstrasse 190, 8057 Zürich, Switzerland.

Elisabeth RushingUniversity Hospital of Zurich, Institute of Neuropathology, Schmelzbergstrasse 12, 8091 Zürich, Switzerland.ORCID 0000-0001-7616-6320

Lukas SommerUniversity of Zurich, Institute of Anatomy, Winterthurerstrasse 190, 8057 Zürich, Switzerland.ORCID 0000-0002-1143-7908

Funding

Schweizerische Arbeitsgemeinschaft fur Klinische Krebsforschung KFS-5391-08-2021Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 310030_192075Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 310030_207801Schweizerischer Nationalfonds zur Furderung der Wissenschaftlichen Forschung 310030_192075Schweizerischer Nationalfonds zur Furderung der Wissenschaftlichen Forschung 310030_207801Swiss Cancer Research Foundation KFS-5391-08-2021Universität Zürich

6 · The paper itself

Abstract

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas with limited therapeutic options. Here, we present a novel sporadic murine model of Nf1 wild-type MPNST, driven by conditional expression of oncogenic BrafV600E and loss of Pten in the glial lineage using the Plp1::CreERT2 driver. This model allows for highly penetrant and rapid tumor induction through spontaneous formation, localized initiation, or cell transplantation. Comparative analysis with Tyr::CreERT2-driven melanoma revealed striking phenotypic divergence despite shared genetic alterations, underscoring the importance of the cell of origin in shaping tumor identity. In this system, MPNST cells show refractory capacities to induce melanocytic trans-differentiation upon melanoma-promoting signaling cues, such as canonical Wnt signaling gain of function or increased of levels of the epigenetic mark H3K27Me3 upon Ezh2 gain of function. Our findings emphasize the significance of lineage context in tumor initiation and provide a foundation for future mechanistic and therapeutic studies.

Indexed as

Nerve Sheath NeoplasmsProto-Oncogene Proteins B-rafPTEN PhosphohydrolaseAnimalsCell TransdifferentiationDisease Models, AnimalEnhancer of Zeste Homolog 2 ProteinHistonesMelanomaMiceBraf protein, mouseEnhancer of Zeste Homolog 2 ProteinHistonesProto-Oncogene Proteins B-rafPTEN PhosphohydrolasePten protein, mouseBrafCancerMouse modelMPNSTPten

Identifiers

PMID41063628

DOI10.1242/dmm.052471

PMCPMC12690522

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.