Project description:Single-cell RNA-Seq was conducted on 19 pediatric high-grade glioma patient samples to study tumor heterogeneity and tumor/immune cell interaction.
Project description:Cultured pediatric high-grade glioma cell lines (SU-DIPG-IV, HSJD-DIPG-007, HSJD-GBM-001,BT 245 (RRID:CVCL_IP13)) were treated with selinexor (Karyopharm Therapeutics) at 5xIC50 for 16 hours or vehicle (0.1% DMSO) followed by bulk RNA-Seq
Project description:HSV G207 and polio:rhinovirus PVSRIPO are two different viral immunotherapies used to treat malignant brain tumors in children. While some patients experience durable survival with these viral immunotherapies, many children have no response. The purpose of this work is to explore these viral immunotherapies in pediatric high grade glioma (pHGG) and medulloblastoma in order to elucidate how tumor response to treatment and to identify putative biomarkers of response and therapeutic targets.
Project description:Pediatric high-grade gliomas (pHGGs), including glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG), are highly morbid childhood brain tumors. Even with treatment, overall survival is poor, making pHGG the number one cause of cancer death in children. Up to 80% of DIPGs harbor a somatic missense mutation in genes encoding Histone H3 proteins. To investigate whether this H3K27M mutation is associated with distinct chromatin structure that alters transcription regulation, we generated the first high-resolution Hi-C maps of pHGG cell lines and tumor tissue. By integrating transcriptome (RNA-Seq), enhancer landscape (ChIP-Seq), genome structure (Hi-C), and chromatin accessibility (ATAC-Seq) datasets from H3K27M mutant and wild-type specimens, we identified tumor specific enhancers and regulatory networks for known oncogenes. In addition, we identified distinct genomic structural variations that lead to enhancer hijacking and gene co-amplification, including A2M, JAG2, FLRT1.