Understanding childhood brain cancers

By Sathya Achia Abraham

A team of Virginia Commonwealth University researchers is studying the underlying causes of brain tumors in children to pinpoint the genetic changes that take place in healthy cells and transform them into cancer.

Through the VCU Medical Center’s Pediatric Brain Tumor Research Program, Timothy E. Van Meter, Ph.D., an assistant professor in the VCU Department of Neurosurgery, and Gary Tye, M.D., a pediatric neurosurgeon at the VCU Medical Center’s Harold F. Young Neurosurgical Center, are looking at the full spectrum of genes that play a role in pediatric brain tumor progression - the leading cause of death from childhood cancer.

Van Meter, Tye and the VCU team have been collaborating with investigators with the Labatt Brain Tumor Center at the Hospital for Sick Kids in Toronto, Canada, on several projects. Using a variety of molecular techniques, the team has been able to look globally at the tumor-specific changes that lead to transformation of normal brain cells into cancerous cells.

“Ultimately, we hope to develop tests that will tell us, based on the patterns of gene alteration in a patient, which tailored treatment they will most benefit from and which treatment protocol will most effectively eradicate their tumor. Our large-scale studies are providing the information we need to do just that,” said Van Meter.

In a study published online the week of March 9 in Nature Genetics, the international team reported the discovery of a molecular pathway that becomes genetically altered, resulting in the growth of a brain tumor called a medulloblastoma. The findings may one day help researchers develop a therapy to target the specific pathway and block the genetic changes from occurring, possibly preventing tumor growth.

According to Van Meter, a medulloblastoma typically originates in the cerebellum and can be extremely aggressive. This area of the brain is responsible for the coordination of voluntary movement and helps maintain balance and muscle tone. Medulloblastomas can cause pressure in the brain and may block the flow of cerebrospinal fluid. Unfortunately, treatment options such as chemotherapy and radiotherapy can cause severe developmental and cognitive deficits in patients.

“Conducting research in pediatric brain tumors is challenging because statistically meaningful, clinically relevant studies require more patient samples than most centers have available to study,” said Van Meter. “Therefore, scientists such as myself form large collaborative networks – like the one we formed for this study – pooling resources and patient materials.” 

In this study, the team examined approximately 200 medulloblastoma specimens and characterized alterations in DNA on chromosomes. The VCU team consulted and provided medulloblastoma clinical samples and data.
Van Meter said that the team continues to examine this large cohort of patient material with other genomic technologies as well, to look at gene expression and other chemical and biological processes at play.

This research involves faculty from the VCU Department of Pathology in the Molecular Diagnostics Laboratory and the Department of Biostatistics.

This work was supported by the American Brain Tumor Association Cherise Fleming Translational Research Grant Award from the Childhood Brain Tumor Foundation and the VCU School of Medicine Harold F. Young Neurosurgical Center.