Medulloblastoma is the most prevalent and aggressive brain tumor in the pediatric population. We have to better understand the mechanisms of tumor formation in all subtypes of medulloblastoma so as to use that knowledge to devise new therapies that will be more efficient and also less toxic than current standard of care.
The role of the BAI1-3 (ADGRB1-3) family of proteins has not been thoroughly examined in medulloblastoma.
We hypothesize that ADGRB1-3 family of adhesion GPCRs can serve as tumor suppressors in the cerebellum and that loss of their expression through epigenetic silencing facilitates medulloblastoma formation. We have found that ADGRB1 is silenced in all 4 groups of medulloblastoma and that its loss of expression reduces p53 expression (Zhu D et al, 2018, Cancer Cell). We have further preliminary data showing that ADGRB3 is silenced exclusively in the WNT group of medulloblastoma and facilitates b-catenin-mediated transformation.
What are the goals of this project?
The goals of this project are to examine the expression of the ADGRB1-3 family of adhesion GPCRs and their binding proteins in medulloblastoma samples of all subtypes and the methylation status of the ADGRB1-3 genes in medulloblastoma of all 4 subtypes.
What is the impact of this project?
Once we will have defined the role of ADGRB1-3 genes in medulloblastoma, we will be in a better position to try to develop epigenetic therapy aimed at reactivating their expression.
Why the CBTN request is important to this project?
Medulloblastoma, while highly malignant are rare tumors and access to specimens is limited. In particular when trying to understand differences between subtypes, one needs to have enough specimens representing each subtype for statistical significance.
The Children's Brain Tumor Network will contribute to this project by providing tumor DNA samples and by providing access to the Pediatric Brain Tumor Atlas.
Medulloblastomas comprises the vast majority of pediatric embryonal tumors and by definition arise in the posterior fossa, where they constitute approximately 40% of all posterior fossa tumors. Other forms of embryonal tumors each make up 2% or less of all childhood brain tumors.The clinic