Patient-derived tumoroids recapitulate the morphologic and molecular features of pediatric brain tumors
Pediatric brain tumors (PBTs) are the leading cause of cancer-related mortality in children. Despite advances in next-generation sequencing (NGS) deepening our understanding of the molecular features of PBT, the lack of preclinical models that capture their complexity and diversity remains a significant barrier to developing less toxic and more effective treatments. We have established 20 ex-vivo patient-derived tumoroid (PDTs) cultures from fresh surgical material of a wide range of PBTs, including low- and high-grade gliomas, medulloblastomas, and even rarer tumor entities such as a CNS tumor with BCOR alteration. Immunofluorescence, NGS analysis, and DNA methylation profiling revealed that the PDTs faithfully mirrored the cellular nature, the genetic and epigenetic landscape of their matched primary tumors. Our study shows the feasibility of generating PDTs, even from rarer entities, that recapitulate the genetic and epigenetic features of primary tumors, highlighting their potential as models for tumor biology studies and precision medicine.
Authors
- Maria Teresa Azevedo
- Roberto Luiz da Silva (ORCID: https://orcid.org/0000-0001-5445-7194)
- Ana Paula Fernandes (ORCID: https://orcid.org/0000-0002-6916-4025)
- Luísa Fonseca (ORCID: https://orcid.org/0000-0003-4208-7370)
- André F. Maia (ORCID: https://orcid.org/0000-0001-5987-7016)
- Joana Peixoto (ORCID: https://orcid.org/0000-0001-9469-5680)
- Jorge Pinheiro (ORCID: https://orcid.org/0000-0003-3099-0984)
- Jorge Lima (ORCID: https://orcid.org/0000-0001-7780-0901)
- Anabela Ferro (ORCID: https://orcid.org/0000-0001-6042-4591)
- Bruno Esteves (ORCID: https://orcid.org/0000-0002-3643-2935)
- Paula Soares (ORCID: https://orcid.org/0000-0001-9607-6998)
- Arnaud Da Cruz Paula (ORCID: https://orcid.org/0000-0001-7694-8760)
- Luiz Lehmann Coutinho (ORCID: https://orcid.org/0000-0002-7266-8881)
- Josué Pereira (ORCID: https://orcid.org/0000-0002-1060-3257)
- MONAIRA CRISTIANE ALCIDES DA COSTA (ORCID: https://orcid.org/0000-0002-2892-928X)
- Joana Oliveira (ORCID: https://orcid.org/0000-0002-9996-1463)
- Yingjie Zhu (ORCID: https://orcid.org/0000-0003-1849-6019)
- Susana Nunes
- Bárbara Soares-Ferreira
Institutions
- Memorial Sloan Kettering Cancer Center (US)
- University of Lisbon (PT)
- Universidade do Porto (PT)
- IPO Porto (PT)
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto (PT)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2025-11-20
- DOI
- https://doi.org/10.1038/s41698-025-01151-w
- Citations
- 1
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.63
Funders
- Universidade do Porto
- Liga Portuguesa Contra o Cancro
- Fundação para a Ciência e a Tecnologia