New Insights into Pediatric Brain Tumor Development Offer Hope for Targeted Therapies
A collaborative research effort involving Baylor College of Medicine, St. Jude Children’s Research Hospital and Texas Children’s Hospital has unveiled a crucial mechanism driving the development of pediatric supratentorial ependymoma (EPN), the third most common pediatric brain tumor. Published in the journal Nature, the findings point to potential new treatment strategies for these aggressive and often chemo-resistant cancers.
“Pediatric brain tumors are often thought to originate early during brain development, but what drives the transformation of normal developing brain cells into cancer cells is incompletely understood,” explained Alisha Kardian, a graduate student in Baylor’s Cancer and Cell Biology program and first author of the study. “We discovered a mechanism that taps into normal brain development to drive tumor growth.”
Understanding ZFTA-RELA Fusion-Positive Ependymoma
The research focused on ZFTA-RELA (ZR) fusion-positive ependymoma, a type of tumor that predominantly affects the brain cortex of young children. These tumors arise from a fusion between the ZFTA and RELA genes, creating an abnormal protein that activates cancer-promoting genes. Baylor College of Medicine
Previously, it remained unclear why this fusion protein caused tumors specifically during early childhood and in certain brain cell types. Researchers hypothesized that the answer lay within the brain’s developmental processes.
How ZR Fusion Protein Hijacks Brain Development
During fetal and early postnatal life, stem-like cells rapidly divide, giving rise to neurons and glial cells. This process involves exposing regions of DNA, making genes accessible for alteration. However, once these stem cells mature, DNA typically tightens its structure, limiting gene expression changes.
The study revealed that the ZR fusion protein doesn’t directly open DNA, but instead exploits the naturally open DNA present in rapidly dividing cells. By interacting with the genetic material, ZR alters gene expression in a way that promotes tumor formation. Nature
Further investigation showed that once activated by ZR, a dominant cancer “founder” clone emerges, creating a heterogeneous tumor that mimics normal brain development but remains in an immature state.
Implications for Future Treatments
“Understanding these developmental vulnerabilities opens the door to new therapeutic approaches aimed at pushing tumor cells toward full differentiation or targeting the early progenitor population that fuels tumor growth,” said Dr. Benjamin Deneen, professor and director of the Center for Cancer Neuroscience at Baylor. Baylor College of Medicine
Dr. Stephen Mack from St. Jude Children’s Research Hospital added that the findings identify specific developmental epigenomic states critical for ZR-driven transformation and how these states shape tumor progression. Nature
About Ependymoma
Ependymoma is a rare type of brain or spinal cord tumor. St. Jude Children’s Research Hospital specializes in the care and treatment of ependymoma in children. St. Jude Children’s Research Hospital