EMBO Molecular Medicine (Oct 2022)
Mesenchymal tumor organoid models recapitulate rhabdomyosarcoma subtypes
- Michael T Meister,
- Marian J A Groot Koerkamp,
- Terezinha deSouza,
- Willemijn B Breunis,
- Ewa Frazer‐Mendelewska,
- Mariël Brok,
- Jeff DeMartino,
- Freek Manders,
- Camilla Calandrini,
- Hinri H D Kerstens,
- Alex Janse,
- M Emmy M Dolman,
- Selma Eising,
- Karin P S Langenberg,
- Marc vanTuil,
- Rutger R G Knops,
- Sheila Terwisscha vanScheltinga,
- Laura S Hiemcke‐Jiwa,
- Uta Flucke,
- Johannes H M Merks,
- Max M vanNoesel,
- Bastiaan B J Tops,
- Jayne Y Hehir‐Kwa,
- Patrick Kemmeren,
- Jan J Molenaar,
- Marc van deWetering,
- Ruben vanBoxtel,
- Jarno Drost,
- Frank C P Holstege
Affiliations
- Michael T Meister
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Marian J A Groot Koerkamp
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Terezinha deSouza
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Willemijn B Breunis
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Ewa Frazer‐Mendelewska
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Mariël Brok
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Jeff DeMartino
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Freek Manders
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Camilla Calandrini
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Hinri H D Kerstens
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Alex Janse
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- M Emmy M Dolman
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Selma Eising
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Karin P S Langenberg
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Marc vanTuil
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Rutger R G Knops
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Sheila Terwisscha vanScheltinga
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Laura S Hiemcke‐Jiwa
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Uta Flucke
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Johannes H M Merks
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Max M vanNoesel
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Bastiaan B J Tops
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Jayne Y Hehir‐Kwa
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Patrick Kemmeren
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Jan J Molenaar
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Marc van deWetering
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Ruben vanBoxtel
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Jarno Drost
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- Frank C P Holstege
- Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
- DOI
- https://doi.org/10.15252/emmm.202216001
- Journal volume & issue
-
Vol. 14,
no. 10
pp. n/a – n/a
Abstract
Abstract 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.
Keywords