Oncohistone Mutations in Diffuse Intrinsic Pontine Glioma

More than 60–70% of DIPG tumors have lysine 27 to methionine mutations (K27M). Histone H3K27M mutations reprogram the epigenome with a global reduction in H3K27 methylation. Sequestering of Polycomb Repressive Complex 2 at poised enhancers by H3K27M mutant proteins represents a mechanism for the global reduction of H3K27 methylation. H3K27M mutation accelerates tumorigenesis, especially for brainstem high-grade gliomas and high-grade DIPG Diffuse intrinsic pontine glioma (DIPG) is a lethal pediatric tumor with no currently available treatment options. More than 60–70% DIPG tumors harbor heterozygous mutations at genes encoding histone H3 proteins that replace lysine 27 with methionine (K27M). In this review, we discuss how K27M mutation reprograms the cancer epigenome to lead to tumorigenesis, and highlight potential drug targets and therapeutic agents for DIPG. Diffuse intrinsic pontine glioma (DIPG) is a lethal pediatric tumor with no currently available treatment options. More than 60–70% DIPG tumors harbor heterozygous mutations at genes encoding histone H3 proteins that replace lysine 27 with methionine (K27M). In this review, we discuss how K27M mutation reprograms the cancer epigenome to lead to tumorigenesis, and highlight potential drug targets and therapeutic agents for DIPG.