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Updated: Jan 30, 2026

Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma
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Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma

Published on: April 11, 2018

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Insight into the Etiology of Undifferentiated Soft Tissue Sarcomas from a Novel Mouse Model

Jonathan T Fleming1, Emily Brignola1, Lei Chen1

  • 1Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee.

Molecular Cancer Research : MCR
|January 27, 2019
PubMed

Insights

Aberrant Hedgehog pathway activation drives sarcoma formation. A novel mouse model reveals GLI2A induces Ewing-like sarcomas from mesenchymal progenitors, linking Hedgehog signaling to undifferentiated soft tissue sarcoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Aberrant Hedgehog signaling is implicated in various cancers, including embryonal rhabdomyosarcoma (eRMS).
  • The precise role of Hedgehog pathway activation in undifferentiated soft tissue sarcoma (STS) etiology requires further elucidation.
  • A well-defined genetic mouse model for Ewing sarcoma, driven by EWS-ETS gene fusions, is lacking.

Purpose of the Study:

  • To develop and characterize a novel mouse model (PCG2) for studying Hedgehog pathway-driven sarcomas.
  • To investigate the phenotypic characteristics of sarcomas induced by GLI2A, a Hedgehog pathway activator.
  • To explore the cellular origins and molecular targets of GLI2A-induced sarcomas.

Main Methods:

  • Generation of the PCG2 mouse model with human GLI2A expression.
  • Histopathological and molecular analysis of induced sarcomas.
  • Comparison of PCG2 sarcomas with eRMS and Ewing sarcoma.

Main Results:

  • PCG2 mice developed undifferentiated sarcomas phenotypically distinct from eRMS.
  • These sarcomas exhibited characteristics reminiscent of Ewing sarcoma, including Nkx2.2 expression.
  • Tumors originated from naïve mesenchymal progenitors, and EWS-ETS gene fusions were absent.

Conclusions:

  • GLI2A-induced sarcomas in PCG2 mice represent a novel model for Hedgehog-driven undifferentiated soft tissue sarcomas.
  • Hedgehog pathway activation, specifically via Gli2, is sufficient to induce Ewing-like sarcomas.
  • This study establishes a direct link between oncogenic Hedgehog activity and the pathogenesis of undifferentiated STS.

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