Open AccessMesenchymal tumor organoid models recapitulate rhabdomyosarcoma subtypes
Author(s) -
Meister Michael T,
Groot Koerkamp Marian J A,
Souza Terezinha,
Breunis Willemijn B,
FrazerMendelewska Ewa,
Brok Mariël,
DeMartino Jeff,
Manders Freek,
Calandrini Camilla,
Kerstens Hinri H D,
Janse Alex,
Dolman M Emmy M,
Eising Selma,
Langenberg Karin P S,
Tuil Marc,
Knops Rutger R G,
Scheltinga Sheila Terwisscha,
HiemckeJiwa Laura S,
Flucke Uta,
Merks Johannes H M,
Noesel Max M,
Tops Bastiaan B J,
HehirKwa Jayne Y,
Kemmeren Patrick,
Molenaar Jan J,
Wetering Marc,
Boxtel Ruben,
Drost Jarno,
Holstege Frank C P
Publication year - 2022
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202216001
Subject(s) - organoid , mesenchymal stem cell , rhabdomyosarcoma , cancer research , biology , computational biology , medicine , pathology , microbiology and biotechnology , sarcoma
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.