Patient-derived tumoroids recapitulate the morphologic and molecular features of pediatric brain tumors

Pediatric brain tumors are the leading cause of cancer-related deaths in children. Although modern genetic technologies have greatly improved our understanding of these tumors, turning this knowledge into safer and more effective treatments remains difficult. One major challenge is the lack of laboratory models that truly reflect the complexity and diversity of childhood brain tumors.

 

In this study, researchers successfully created 20 patient-derived “tumoroid” models grown in the laboratory from fresh tumor samples collected during surgery. These miniature tumor models represent a wide range of pediatric brain tumors, including low- and high-grade gliomas, medulloblastomas, and even very rare tumor types.

 

Detailed analyses showed that these tumoroids closely matched the original tumors from each patient, not only in their cellular makeup but also in their genetic and molecular characteristics. Importantly, the team demonstrated that it is possible to generate accurate models even from rare pediatric brain tumors.

 

These findings highlight the potential of patient-derived tumoroids as powerful tools to study how pediatric brain tumors grow and respond to treatment. In the future, such models could help researchers test therapies more effectively and move closer to personalized, less toxic treatments for children with brain tumors.

Bárbara Soares-Ferreira ^{1 2}, Joana Peixoto ¹, Anabela Ferro ³, Beatriz Esteves ^{1 4,} Jorge Pinheiro ⁵, Roberto Silva ^{4 5}, Josué Pereira ^{4 5}, Joana Oliveira ⁵, Arnaud Da Cruz Paula ¹, Yingjie Zhu ⁶, Maria Teresa Azevedo ³, Luísa Fonseca ³, Lara Coutinho ³, André Filipe Maia ¹, Paula Soares ^{1 3 4}, Susana Nunes ⁵, Ana Paula Fernandes ⁵, M J Gil Da Costa ⁵, Jorge Lima ^{7 8 9}

¹ i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.

² FMUL-Faculdade de Medicina da Universidade de Lisboa, Universidade de Lisboa, Lisboa, Portugal.

³ IPATIMUP-Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal.

⁴ FMUP-Faculdade de Medicina da Universidade do Porto, Porto, Portugal.

5 CHUSJ-Centro Hospitalar Universitário São João, Porto, Portugal.

⁶ Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, Portugal.

⁷ i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal. 

⁸ IPATIMUP-Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal. 

⁹ FMUP-Faculdade de Medicina da Universidade do Porto, Porto, Portugal. 

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.