Researchers from the University of British Columbia (UBC) and BC Cancer, in collaboration with BC Children’s Hospital Research Institute (BCCHR), have developed a new test to more easily diagnose medulloblastoma, the most common malignant brain tumor in children.
The test, which can distinguish between extremely high-risk medulloblastoma cases requiring radiation therapy and those at lower risk and not requiring radiation, could pave the way for personalized treatment options for children suffering from the disease.
“With this new test, more doctors may one day identify children with the most aggressive forms of medulloblastoma and better tailor treatment,” said the study’s senior author, Dr. Poul Sorensen, professor of pathology and laboratory medicine on the faculty of UBC. medicine, leading scientist at BC Cancer and associate member at BCCHR.
At the moment, according to the researchers, only sophisticated and expensive tests conducted in a handful of labs around the world can identify children with the most aggressive forms of the disease, which forms in the cerebellum, the back part of the brain.
Given current testing limitations, all children with medulloblastoma receive the same type of treatment, meaning that children with less aggressive forms are unnecessarily exposed to toxic side effects of brain radiotherapy and chemotherapy, often leading to permanent learning, physical and emotional disabilities. Meanwhile, children with the most aggressive forms of the disease may not receive treatments sufficient to cure the disease.
The new test – developed in Dr. Poul Sorensen at the BC Cancer Research Institute – is based on an antibody-based technique called immunohistochemistry, which is widely available in clinical labs around the world.
Using a technique available in virtually all clinical labs, our new test has the potential to improve the diagnosis and future treatment of pediatric medulloblastoma in nearly every corner of the planet.”
dr. Alberto Delaidelli, MD, lead author of the study. UBC PhD student in Dr. Sorensen
To develop the test, the researchers analyzed several sets of data, including proteomics (which measures overall protein expression in tumor tissues) and transcriptomics (which measures overall gene expression in tumor tissues). Using this strategy, they found a protein called TPD52 that is highly expressed in the most aggressive medulloblastoma.
They then screened for the expression of this protein in about 400 medulloblastoma samples and found that tumors where this protein was easily detectable were significantly more likely to exhibit aggressive behavior and relapse.
“Today, researchers often move from simpler techniques to extremely complicated ‘omics’ techniques as part of their research efforts to make clinically relevant observations,” said Dr. Delaidelli. “Instead, we used a bit of ‘reverse engineering’, working backwards by analyzing very complicated data sets to develop a technique that can be performed in virtually all clinical labs worldwide.”
The study, recently published in Clinical Cancer Research, is the result of a collaboration between researchers in Vancouver, Toronto, Philadelphia, Heidelberg and Moscow.
The research groups are now testing the test’s performance in a clinical trial, in collaboration with colleagues in Germany and other parts of the world.
University of British Columbia
Delaidelli, A., et al. (2021) Clinically traceable outcome prediction of non-WNT/non-SHH medulloblastoma based on TPD52 immunohistochemistry in a multicohort study. Clinical cancer research. doi.org/10.1158/1078-0432.CCR-21-2057.