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

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

SUBMITTER: Debbache J 

PROVIDER: S-EPMC12690522 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature