Gene Expression Profile of Radiation Therapy Resistant BRAFV600E Pediatric Gliomas

Inhibitors of the MAPK pathway (MAPKi) have shown significant activity in treatment of childhood BRAF-activated brain tumors. However, for tumors harboring BRAFV600E mutations, the drugs are rarely curative, and patients can become refractory to treatment. Combining MAPKi with low dose X-ray therapy (XRT) has the potential to improve the cure rate, but development of XRT resistance poses a major challenge. To understand the mechanisms of radiation resistance in BRAFV600E type pediatric low-grade gliomas, radiation resistance models were developed by using BT-40 pediatric low-grade glioma (PLGG) PDX model harboring BRAFV600E mutation. RNA sequencing was performed to determine the gene expression profile of primary tumors and resistant tumors. Each tumor tissue was transplanted to 3 scid mice respectively. When tumor volume reach ~0.3~0.6 cm3, tumor tissue (from three mice, triplicates) were collected and were snap-frozen in liquid nitrogen. RNA was isolated and applied to subsequent 100bp paired read sequencing run with Illumina NovaSeq 6000 platform at 100 bp paired-end module. Overall design: Each tumor tissue was transplanted to 6-8 weeks old female scid mice. Tumor tissue were harvested when tumor size reach 0.3~0.6cm^3, RNA was isolated and applied to subsequent 100bp paired read sequencing run with Illumina NovaSeq 6000 platform at 100 bp paired-end module. BT40: Classified as PDX, primary. This sample group represents the primary model of pediatric glioma without any treatment. BT40X: Classified as PDX, X-radiation therapy resistant. This group includes samples from the primary model that have been exposed to radiation therapy and have exhibited resistance.