Study Investigates Potential Embryonic Origin of Medulloblastomas

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Medulloblastomas may exist in a premalignant form at birth after initially developing during the first or second trimester of pregnancy, according to a new international study published by Hendrikse et al in Nature. As medulloblastomas typically present around age 7, the team’s discovery is the first indication there could be a window of several years during which a medulloblastoma could be preventable.

Brain tumors account for 20% of all new pediatric cancer cases and are the deadliest form of childhood cancer. Up to 40% of patients succumb to the disease, while survivors must deal with the long-term toxicities associated with aggressive surgery, chemotherapy, and radiation of the whole brain and spinal cord. 

Leading research groups at the Max Rady College of Medicine at the University of Manitoba, the National Cancer Center in Tokyo, the Seattle Children’s Research Institute, and The Hospital for Sick Children (SickKids) partnered to study Group 4 medulloblastomas, the most common and least understood subgroup. The study team’s goal was to identify how and where group 4 tumors arise during embryonic development in the hopes of accelerating discoveries of more effective treatments. 

Worldwide Collaboration Shows Where and How Medulloblastomas Develop

The researchers collected medulloblastoma samples from children’s hospitals around the world and used several sequencing technologies to successfully identify genetic variations that can cause group 4 medulloblastomas. They found that these genetic variations were effectively “stalling” normal cellular differentiation in a specific cell type only present during early fetal development of the human cerebellum. This “stalling” of normal cellular differentiation results in a premalignant form of the tumor that then resides in the brain after birth, a finding which may apply to the other forms of medulloblastomas.  

The researchers note that the cell type they identified is far more common in humans and is found in a region of the developing cerebellum that is more structurally complex than in other mammals. They say this could mean medulloblastomas are a direct consequence of the evolved complexity of the human cerebellum. 

Crucially, the team’s findings show that medulloblastomas originate much earlier in pregnancy than previously thought and have identified for the first time that they could even be preventable. They say clinicians may have a window of opportunity between birth and symptom onset to detect medulloblastomas before they develop, and possibly prevent them from turning into deadly brain tumors.

“Our success was only possible because of the amazing international team involving a wide range of clinical and basic scientific expertise. Central to the study were extensive comparisons of normal and tumor tissue to enable rapid identification of the genes and cells that go awry to cause these tumors. Studies in cultured cells were then essential to confirm our findings. We are excited to continue to work together to develop precision therapies for affected children,” says Kathleen Millen, PhD, a Professor and Principal Investigator at the Center for Integrative Brain Research at the Seattle Children’s Research Institute.  

Disclosure: This work was supported by the National Institutes of Health, Stand Up To Cancer, the Canadian Institutes of Health Research, Fonds de Recherche du Québec–Santé, The Natural Sciences and Engineering Research Council of Canada (NSERC), CancerCare Manitoba Foundation, the National Cancer Center Research and Development Funds, and SickKids Foundation. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.