Mesenchymal tumor organoid models recapitulate rhabdomyosarcoma subtypes.

Autor: Meister MT; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., Groot Koerkamp MJA; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., de Souza T; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., Breunis WB; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Department of Oncology and Children's Research Center, University Children's Hospital Zürich, Zürich, Switzerland., Frazer-Mendelewska E; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., Brok M; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., DeMartino J; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., Manders F; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., Calandrini C; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., Kerstens HHD; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Janse A; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Dolman MEM; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Children's Cancer Institute, Lowy Cancer Centre, UNSW Sydney, Kensington, NSW, Australia.; School of Women's and Children's Health, Faculty of Medicine, UNSW Sydney, Kensington, NSW, Australia., Eising S; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Langenberg KPS; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., van Tuil M; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Knops RRG; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., van Scheltinga ST; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Hiemcke-Jiwa LS; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Flucke U; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Merks JHM; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., van Noesel MM; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Tops BBJ; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Hehir-Kwa JY; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Kemmeren P; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Center for Molecular Medicine, UMC Utrecht and Utrecht University, Utrecht, The Netherlands., Molenaar JJ; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., van de Wetering M; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., van Boxtel R; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., Drost J; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Oncode Institute, Utrecht, The Netherlands., Holstege FCP; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Center for Molecular Medicine, UMC Utrecht and Utrecht University, Utrecht, The Netherlands.
Jazyk: angličtina
Zdroj: EMBO molecular medicine [EMBO Mol Med] 2022 Oct 10; Vol. 14 (10), pp. e16001. Date of Electronic Publication: 2022 Aug 02.
DOI: 10.15252/emmm.202216001
Abstrakt: Rhabdomyosarcomas (RMS) are mesenchyme-derived tumors and the most common childhood soft tissue sarcomas. Treatment is intense, with a nevertheless poor prognosis for high-risk patients. Discovery of new therapies would benefit from additional preclinical models. Here, we describe the generation of a collection of 19 pediatric RMS tumor organoid (tumoroid) models (success rate of 41%) comprising all major subtypes. For aggressive tumors, tumoroid models can often be established within 4-8 weeks, indicating the feasibility of personalized drug screening. Molecular, genetic, and histological characterization show that the models closely resemble the original tumors, with genetic stability over extended culture periods of up to 6 months. Importantly, drug screening reflects established sensitivities and the models can be modified by CRISPR/Cas9 with TP53 knockout in an embryonal RMS model resulting in replicative stress drug sensitivity. Tumors of mesenchymal origin can therefore be used to generate organoid models, relevant for a variety of preclinical and clinical research questions.
(© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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