Genomics and Oncogenesis of Pediatric Brain Tumors

Objectives and Challenges

The team was formed to conduct research on infiltrating brainstem gliomas and the oncogenetics of brain tumors in particular. As part of the Paris Kids Cancer and Cell-ID consortia, its activities span the continuum from basic to clinical research. Its work relies on patient-derived experimental models (cell cultures, organoids, orthotopic xenografts) as well as genetically modified syngeneic models. This integrated approach is supported by robust translational research conducted by several investigators from Gustave Roussy and Necker Hospital who are affiliated with the team.

Research Areas / Major Projects

Research has expanded to include other pediatric brain tumors that share characteristics with infiltrating gliomas, notably tumor invasion (Gliomatosis Cerebri) or alterations in the PRC2 complex (Ependymomas). The research is organized around three main areas:

1. The early stages of oncogenesis and cellular dysregulation in the development of these tumors (epigenetics and analysis of secondary events);

2. Treatment resistance and the identification of new targets through genetic screening;

3. Tumor–microenvironment interactions and invasion mechanisms.

Two emerging areas complement this research: Oncogenetics, including the study of tumor predispositions and their modeling using autologous brain organoids; Liquid biopsies, focused on the analysis of cerebrospinal fluid and biomarkers such as circulating tumor DNA for diagnosis and treatment monitoring.

Major Findings, Prospects, and Scientific, Clinical, and Societal Impacts

The team has contributed to major advances: participation in the WHO classification of diffuse midline gliomas, identification of prognostic and theranostic markers, demonstration of the role of MAP kinases in oncogenesis and tumor invasion, and the study of predisposition syndromes.

Ultimately, this research aims to identify new biomarkers and therapeutic strategies in order to develop precision medicine trials and improve survival and quality of life for children with these tumors, which remain largely incurable.