Biological and prognostic relevance of epigenetic regulatory genes in high-grade gliomas (HGGs)

• DOI: 10.17615/cjne-g668
• Publication Date: 2024-01-01
• Authors: Hinton, Andrew; Kesari, Santosh; Xiu, Joanne; Sumrall, Ashley Love; Aulakh, Sonikpreet; Darabi, Sourat; Ashley, David M; Glantz, Michael J; Sengupta, Soma; Spetzler, David; Demeure, Michael J

Background High-grade gliomas (HGGs) are the most aggressive type of gliomas and have the poorest outcomes. Chromatin remodeling (CR) genes have been implicated in multiple oncogenic pathways in numerous cancer types. In gliomagenesis, CR genes have been implicated in regulating stemness of glioma cells, the tumor microenvironment (TME), and resistance to therapies. Methods We performed molecular profiling of 4244 HGGs and evaluated associations of CR mutations with other cancer related biomarkers, infiltration by immune cells, and immune gene expression. We also evaluated the association between CR mutations and survival in IDH WT HGG patients. Results Nearly 10% of HGGs carry mutations in CR genes, with higher prevalence (15%) in HGGs with IDH mutations. Analysis of co-occurrence with other biomarkers revealed that CR-mutated HGGs possess favorable genetic alterations which may have prognostic value. CR-mutated HGGs with wild type IDH demonstrated colder TME and worse OS overall compared to the CR-wild type HGGs. Conclusions Our study reveals the prognostic effects of CR mutations in HGG and points to several biomarker candidates that could suggest sensitivity to emerging therapeutic strategies.