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Human malignant peripheral nerve sheath tumors have a molecular counterpart in canines

ABSTRACT: Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas with poor prognosis in humans and dogs. Their rarity and heterogeneity in humans limit molecular characterization and therapeutic advances. Here, we investigated whether canine MPNST mirror human molecular subgroups. Using laser-capture microdissection and RNA sequencing, we profiled 20 canine MPNST and identified two distinct transcriptional clusters (C1, C2) with differing gene expression, histopathology, and marker profiles. C1 tumors exhibited Schwann cell–like features, while C2 showed precursor-like characteristics. Cross-species analysis revealed strong conservation of gene expression and demonstrated that canine C1 corresponds to human G2, whereas C2 aligns with G1. Pathway analysis showed SHH signaling activation and increased cell cycle activity in C2, and non-canonical WNT and PI3K–AKT–mTOR signaling in C1. These findings represent the largest transcriptomic study of canine MPNST to date and establish strong molecular parallels with human disease, supporting their use as a translational model for therapeutic development.

ORGANISM(S): Canis lupus familiaris

PROVIDER: GSE325901 | GEO | 2026/09/23

REPOSITORIES: GEO

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