Epigenetic and Metabolic Changes in Diffuse Intrinsic Pontine Glioma

Abstract

Diffuse midline glioma (DMG), hitherto known as diffuse intrinsic pontine glioma (DIPG), is a rare and aggressive form of brain cancer that primarily affects children. Although the exact cause of DMG/DIPG is not known, a large proportion of DMG/DIPG tumors harbor mutations in the gene encoding the histone H3 protein, specifically the H3K27M mutation. This mutation decreases the level of H3K27me3, a histone modification that plays a vital role in regulating gene expression through epigenetic regulation. The mutation also alters the function of polycomb repressive complex 2 (PRC2), thereby preventing the repression of genes associated with cancer development. The decrease in H3K27me3 caused by the histone H3 mutation is accompanied by an increase in the level of H3K27ac, a post-translational modification related to active transcription. Dysregulation of histone modification markedly affects gene expression, contributing to cancer development and progression by promoting uncontrolled cell proliferation, tumor growth, and metabolism. DMG/DIPG alters the metabolism of methionine and the tricarboxylic acid cycle, as well as glucose and glutamine uptake. The role of epigenetic and metabolic changes in the development of DMG/DIPG has been studied extensively, and understanding these changes is critical to developing therapies targeting these pathways. Studies are currently underway to identify new therapeutic targets for DMG/DIPG, which may lead to the development of effective treatments for this devastating disease.

Epigenome-Driven Strategies for Personalized Cancer Immunotherapy

“… 3 When tumor suppressor genes are silenced, cells can continue to divide uncontrollably, leading to the formation of a tumor. 4 …”

“… 1 This is a complex and multifactorial process that can involve changes in multiple genes and pathways and is only beginning to be understood. 4 …”

“…Non-coding RNAs (ncRNAs) are RNA molecules that are not translated into proteins but play important roles in gene regulation. 2 , 4 Aberrant expression of ncRNAs, such as microRNAs and long non-coding RNAs, has been observed in various types of cancer and can contribute to oncogenesis by promoting cell proliferation, invasion, and metastasis. Epigenetic changes, including DNA methylation and histone modifications, can also alter the expression of cancer-related genes and contribute to tumor initiation and progression.…”