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Defining the origin of medulloblastomas

Researchers at St. Jude Children’s Hospital uncover the origins of medulloblastoma subgroup using single cell sequencing.

Medulloblastoma is the most common high-grade brain tumour in children, accounting for 15-20% of all childhood brain tumours.

Previous studies have identified four distinct subgroups of medulloblastoma (WNT, SHH, Group 3 and Group 4) each with different genomic profiles, patient demographics and treatment outcomes. All medulloblastomas occur in the cerebellum, a region of the brain located at the base of the skull, just above the brainstem.

The association between genomic profiles and the patient’s age at diagnosis suggests that medulloblastoma subgroups arise from different cell types, and at different stages of a child’s development.

The cellular origins of the different subgroups has only been partially investigated. Earlier studies suggest SHH-subtype medulloblastomas develop from a subset of cells called cerebellar granule neuron progenitor cells (also known as GNPs), whereas WNT-subtype medulloblastomas are thought to develop from cells within a specific area of the developing brain, known as the lower rhombic lip.

In contrast, the source of Group 3 and Group 4 medulloblastomas, which account for approximately 60% of all medulloblastomas, is unclear.

Using a technique called single-cell RNA sequencing, researchers at St. Jude Children’s Hospital have mapped gene expression profiles in thousands of individual cells from 25 medulloblastoma tumour samples, to compare these cells to normal cells within the developing cerebellum.

Through this approach, the team were able to identify two types of cells (unipolar brush cells and glutamatergic cerebellar nuclei cells) as possible cells-of-origin for Group 4 medulloblastomas. When comparing cells from Group 3 medulloblastomas to the normal cells within the cerebellum, the team found no clear similarities.

These results suggests these tumours originate from cells from another area of the brain, but further research is needed to confirm this.

Dr Laure Bihannic, co-first author of this study, says “Results from this study are pivotal, as they advance our understanding of the cellular composition of medulloblastoma subgroups. Being able to determine the origins of medulloblastoma subgroups will help us create better pre-clinical models for this tumour type, especially for the poorly understood Group 4 medulloblastoma. These models will help improve therapeutic testing to bring new treatments to the clinic.”

If you require additional information, please contact the Research Team at research@thebraintumourcharity.org 

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