Glioma Development Linked to Methylation Marks in Mouse Model

In a paper appearing in Cell, a team from the Dana-Farber Cancer Institute, Harvard Medical School, the Broad Institute, and Massachusetts General Hospital report on methylation changes found in human IDH-mutant glioma cases that appear to prompt development of the brain cancer in a mouse model of the disease. With CRISPR-based gene editing, the researchers delved into recurrent epigenetic changes near the PDGFRA oncogene and the CDKN2A tumor suppressor gene in mouse oligodendrocyte progenitor cells, showing that the glioma-linked changes led to enhanced PDGFRA activity and CDKN2A silencing that stemmed from altered interactions involving insulator and enhancer regions. "Our study demonstrates that the disruption of an insulator and topological boundary can drive oncogene expression and gliomagenesis in vivo and provides a framework for modeling and functionally characterizing oncogenic regulatory alterations going forward," they write, adding that "[f]uture studies are needed to further characterize the PDGFRA locus and its regulation in developing brain tissue and tumors, as well as to identify and characterize other epigenetic lesions that drive tumorigenesis."