Abstract IA18: Epigenetic addiction in pediatric high-grade gliomas

A remarkably rapidly expanding body of literature points to the epigenome as a new previously unsuspected mechanism of oncogenesis and another “hallmark of cancer.” Indeed, in a large number of cancers, aberrant epigenetic states occur through different mechanisms including altered DNA methylation, covalent histone modification, the reading of these histone modifications by protein regulation modules, histone exchange, chromatin remodelers, or via the effects of non-coding RNAs. Although mutations are also found in canonical signaling pathway genes, we and others identified chromatin-associated proteins to be more commonly altered by somatic alterations than any other class of oncoprotein in several subgroups of childhood high-grade brain tumors. Furthermore, as these childhood malignancies carry fewer non-synonymous somatic mutations per case in contrast to most adult cancers, these mutations are likely drivers in these tumors. Herein, we will use as examples of this novel hallmark of oncogenesis high-grade astrocytomas, including glioblastoma, and a subgroup of embryonal tumors, embryonal tumor with multilayered rosettes (ETMR) to describe the novel molecular defects uncovered in these deadly tumors. We will further discuss evidence for their profound effects on the epigenome and their links to brain development. Importantly, the type, timing and spatial clustering of these molecular alterations provide a better understanding of the pathogenesis of the respective brain ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Mutational Landscape in Brain Tumors Source Type: research