Pediatric high grade gliomas (pHGG) are a devastating disease. In recent years it has become evident that pHGG dramatically differs genetically and molecularly from adult HGG and different drivers have been identified for each. Chemotherapeutics and targeted agents used in adult glioblastoma studies have not been shown to benefit such tumors in the pediatric population. To develop therapies for patients with pHGG, researchers must study how mutations in specific genes may cooperate. Researchers in this field also must discover which pathways are key for tumor progression so they can be targeted by therapeutics. For this project, researchers are focusing on a subset of pHGG that are driven by an activated RAS pathway due to mutations in the genes NF1, SETD2, and/or ATRX. These mutations also often occur together and can promote tumor growth and survival. The goals of this project are to deconstruct how SETD2 and ATRX mutation drives pHGG formation, investigate therapeutic sensitivities of pHGG, and determine if loss of NF1, ATRX or SETD2 alters the tumor immune microenvironment. The Children’s Brain Tumor Network has a large number of pHGG cell lines and specimens that are not available elsewhere and will be integral to this work.
What are the goals of this project?
Researchers on this project will explore how cancer hijacks our cell’s normal growth signals and mutates them to drive pHGG formation and survival in an effort to highlight opportunities for therapeutic advancement.
What is the impact of this project?
By answering the questions posed by researchers, this project could lead to great advancements in potential new therapeutic approaches.
Why is the CBTN request important to this project?
Specimens of the subtype and quality necessary for this work are rare, making the Children’s Brain Tumor Network’s provision of such samples integral.
The Children's Brain Tumor Network contributed to this project by providing cell lines and tissue for cell line generation.
Sandro Santagata, Harvard Medical School
Thomas De Raedt, PhD
Dr. De Raedt researches pediatric high grade glioma development and aims to understand the involvement of crucial pathways. He investigates pathway interaction, and explores ways to develop therapies through analyzing human tumors, performing cellular studies, and developing accurate mouse models. T
Children’s Hospital of Philadelphia
Children’s Hospital of PhiladelphiaJoined on
Operations Center for the Children’s Brain Tumor Tissue Consortium, the Children’s Hospital of Philadelphia (CHOP) is currently ranked 1st nationally for their Pediatric Cancer Program by U.S. News & World Report. CHOP’s Biobank is home to the CBTTC’s pediatric brain and CNS tumor biorepository; the
High-grade Gliomas (HGG) or astrocytomas in children nearly always result in a dismal prognosis. Although novel therapeutic approaches are currently in development, preclinical testing has been limited, due to a lack of pediatric-specific HGG preclinical models. These models are needed to help test
Cooperating Mutations in Brain Tumors of Patients with NF1
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All Brain Tumor Types
Thomas De Raedt