Pediatric Neuro-Oncology and Tumor Genetics

Pediatric neuro-oncology encompasses the study and treatment of brain and spinal cord tumours arising in children, which range from low-grade gliomas and glioneuronal tumours to high-grade gliomas and embryonal malignancies such as medulloblastoma. Over the past decade, advances in tumour genetics have revealed that many paediatric central nervous system neoplasms are defined not only by their histological appearance but by specific molecular alterations. Receptor tyrosine kinase fusions (for example ALK, ROS1, NTRK and MET) and MAPK-pathway mutations underpin distinct biological subgroups with characteristic prognoses and therapeutic vulnerabilities. Epigenetic profiling, particularly DNA methylation analysis, has refined classification schemes, distinguishing infant-type hemispheric gliomas from desmoplastic infantile gangliogliomas and other entities. Integration of genomic, transcriptomic and histopathological data now underlies precision medicine approaches, enabling the rational deployment of targeted inhibitors against BRAF, MEK and TRK proteins and informing clinical trial design. Key challenges include overcoming blood–brain barrier penetration, managing treatment resistance and minimising long-term toxicities in a developing nervous system. Globally, the deepening understanding of paediatric tumour genetics promises to standardise diagnosis, improve risk stratification and broaden access to novel therapies across diverse healthcare settings.

Research from Nature Portfolio

A seminal genomic analysis of an international cohort of infant gliomas revealed three clinical subgroups with divergent outcomes. Tumours in the cerebral hemispheres often harboured single-event fusions in receptor tyrosine kinases (ALK, ROS1, NTRK and MET), conferring an intermediate prognosis. A second subgroup, driven by RAS/MAPK pathway mutations in hemispheric gliomas, exhibited excellent long-term survival, while a third, midline-located group with similar pathway alterations progressed rapidly and failed to respond to conventional chemoradiation. These findings established a molecular framework for individualised therapeutic strategies in infant gliomas and underscored the need for specialised treatment pathways.

Pediatric Neuro-Oncology and Tumor Genetics publication trend

The graph below shows the total number of articles in pediatric neuro-oncology and tumor genetics across all publications each year (not limited to Nature Index journals).

Technical terms

Fusion gene: A hybrid gene created by joining parts of two separate genes, often resulting in aberrant signalling that drives tumour growth.

Receptor tyrosine kinase (RTK): A class of cell-surface receptors that transmit growth signals into cells and are frequently altered in paediatric brain tumours.

Epigenetic profiling: The analysis of chemical modifications to DNA, such as methylation, to classify tumours beyond their genetic sequence.

Progression-free survival: The period during which a patient’s disease remains stable without evidence of progression, used to assess treatment efficacy.

References

1. Capmatinib is an effective treatment for MET-fusion driven pediatric high-grade glioma and synergizes with radiotherapy. Molecular Cancer (2024).
2. Clinical, pathologic, and genomic characteristics of two pediatric glioneuronal tumors with a CLIP2::MET fusion. Acta Neuropathologica Communications (2024).
3. A comprehensive analysis of infantile central nervous system tumors to improve distinctive criteria for infant‐type hemispheric glioma versus desmoplastic infantile ganglioglioma/astrocytoma. Brain Pathology (2023).
4. Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas. Nature Communications (2019).