Establishment of 6 pediatric rhabdomyosarcoma patient’s derived xenograft models closely recapitulating patients’ tumor characteristics

Author:

Gasparini Patrizia1ORCID,Casanova Michela2,Centonze Giovanni3,Borzi Cristina1ORCID,Bergamaschi Luca2,Collini Paola4,Testi Adele5,Chiaravalli Stefano2,Massimino Maura2,Sozzi Gabriella1,Ferrari Andrea2ORCID,Moro Massimo1ORCID

Affiliation:

1. Tumor Genomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

2. Paediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

3. First Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

4. Soft Tissue and Bone Pathology, Histopathology and Pediatric Pathology Unit, Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

5. Laboratory of Molecular Pathology, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Abstract

Introduction: The prognosis for patients with metastatic and recurrent pediatric rhabdomyosarcoma (RMS) remains poor. The availability of preclinical models is essential to identify promising treatments We established a series of pediatric RMS patient derived xenografts (PDXs), all faithfully mirroring primary tumor characteristics and representing a unique tool for clarifying the biological processes underlying RMS progression and relapse. Methods: Fresh tumor samples from 12 RMS patients were implanted subcutaneously in both flanks of immunocompromised mice. PDXs were considered as grafted after accomplishing three passages in mice. Characterization of tumor tissues and models was performed by comparing both morphology and immunoistochemical and fluorescence in situ hybridization (FISH) characteristics. Results: Six PDXs were established, with a successful take rate of 50%. All models closely mirrored parental tumor characteristics. An increased grafting rate for tumors derived from patients with worse outcome (p = 0.006) was detected. For 50% PDXs grafting occurred when the corresponding patient was still alive. Conclusion: Our findings increase the number of available RMS PDX models and strengthen the role of PDXs as useful preclinical tools for patients with unmet medical needs and to develop personalized therapies.

Funder

Associazione Bianca Garavaglia

Publisher

SAGE Publications

Subject

Cancer Research,Oncology,General Medicine

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