Modeling pediatric low-grade glioma heterogeneity using human forebrain organoids
Pediatric low-grade gliomas (pLGGs) are the most common type of brain tumors in children, characterized by their typically slow growth and oncogene-induced senescence. Preclinical models provide the opportunity to investigate the effects of various treatments in a controlled setting before they are tested in human patients; however, reliable models for pLGGs are limited. Here we developed two organoid models for pLGGs, which, after engraftment into mice, exhibited low-grade features. Furthermore, the genome-wide DNA methylation and RNA profiles of the organoids demonstrated closer similarity to low-grade glioma entities compared to high-grade counterparts. Additionally, pLGG organoid-derived cells align with oligodendrocyte-like, astrocyte-like and MAPK signature clusters seen in patient tumors, indicating that the organoids generate a heterogeneous population of cancer cells, where cellular diversity may influence disease progression and treatment response.
Authors
- Toma Tebaldi (ORCID: https://orcid.org/0000-0002-0625-1631)
- Luca Tiberi (ORCID: https://orcid.org/0000-0002-5983-3782)
- Marina Cardano (ORCID: https://orcid.org/0000-0003-0368-3196)
- Chiara Lago (ORCID: https://orcid.org/0000-0002-1317-7847)
- Lucia Santomaso
- Luana Abballe (ORCID: https://orcid.org/0000-0003-4446-2293)
- Davide Pernici (ORCID: https://orcid.org/0000-0002-2728-2306)
- Matteo Gianesello (ORCID: https://orcid.org/0000-0002-8976-6883)
- Celeste Antonacci (ORCID: https://orcid.org/0000-0003-2872-5401)
- Francesco Antonica (ORCID: https://orcid.org/0000-0001-9359-9689)
- Francesca Romana Buttarelli (ORCID: https://orcid.org/0000-0001-5892-1281)
- Manila Antonelli (ORCID: https://orcid.org/0000-0002-9535-931X)
- Linda Petrucci (ORCID: https://orcid.org/0000-0002-6552-4919)
- Simone Minasi (ORCID: https://orcid.org/0000-0002-8872-6409)
- Emma Busarello (ORCID: https://orcid.org/0009-0009-7731-9777)
- Alessia Soldano (ORCID: https://orcid.org/0000-0002-3120-9929)
- Sara Patrizi (ORCID: https://orcid.org/0000-0003-1898-1516)
- G. Leva (ORCID: https://orcid.org/0000-0003-1147-700X)
- Noemi Pozza
- Federica Ress (ORCID: https://orcid.org/0009-0004-4583-2086)
- Gabriele Trentini
- Elisabetta Ferretti
- Francesca Gianno
- Federico Cocchini
- Evelina Miele
- Martina Iannuzzi
Institutions
- Scuola Internazionale Superiore di Studi Avanzati (IT)
- University of Trento (IT)
- Yale Cancer Center (US)
- Istituto Neurologico Mediterraneo (IT)
- Bambino Gesù Children's Hospital (IT)
- Sapienza University of Rome (IT)
Publication Details
- Journal
- Molecular Cancer
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1186/s12943-026-02612-x
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Science Foundation
- EMBO
- Associazione Italiana per la Ricerca sul Cancro