Abstract PR03: The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma

Pediatric high-grade glioma (HGG) remains a tremendous clinical challenge, with a two-year survival of less than 20%. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs) by whole-genome, whole-exome, and/or transcriptome sequencing. Somatic mutations in the bone morphogenetic protein (BMP) receptor ACVR1 occurred in 32% of DIPG, a finding exclusive to brainstem HGG. Structural variants generating fusion genes were found in 47% of pediatric HGG, with recurrent fusions involving the neurotrophin receptor genes NTRK1, 2, or 3 in 40% of infant NBS-HGGs and 5% of pediatric HGG overall. Multiple mutations targeted pathways involving histone modification or chromatin remodeling, cell cycle regulation and receptor tyrosine kinase/RAS/PI3K signaling, in both DIPG and NBS-HGGs at frequencies of greater than 39% in the entire cohort. The HGG mutation burden ranged from 2 non-silent mutations in an infant HGG to more than a million mutations in a tumor associated with germline mismatch repair deficiency. From these findings, we have established novel tumor models to better understand this devastating disease. This work provides new insight into the genetic events driving pediatric HGG tumorigenesis. This abstract is also presented as Poster B14. Citation Format: Alexander K. Diaz, Gang Wu, Barbara S. Paugh, Yongjin Li, Xiaoyan Zhu, Sherri Rankin, Chunxu Qu, Xiang Chen, Junyuan Zhang, John Easton, Michael Edmonson, Charles ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Brain Tumors Source Type: research