RP58 and SMARCB1 in AT/RT Pathogenesis

Atypical teratoid rhabdoid tumor (ATRT) is a common and hard to treat form of pediatric brain cancer. Despite current therapy options including aggressive chemotherapy, radiation, and stem cell transplant, the overall survival rate of ATRT patients is still low. To better treat this disease, researchers must better understand its genetic and molecular characteristics. Researchers have identified genetic alterations that are hallmarks of ATRT. Mutations in a gene named SMARCB1 may lead cells to act like stem cells and become cancerous. Researchers have also identified the transcription factor RP58 (aka ZBTB18) as an essential regulator of brain development. Experiments have been performed to better understand the potential impact on ATRTs. The overall research hypothesis is that RP58 acts with SMARCB1 to control brain development and that disruption of this interaction leads to defects in this process that results in ATRTs. The Children’s Brain Tumor Network provides researchers with the rare ATRT cell lines necessary to complete this work. Understanding the role and regulation of SMARCB1 during early brain development is critical to not only a better understanding of AT/RT tumors but also to the development of novel therapies for this aggressive tumor.