While cancers often originate from mutations and other alterations of cells' DNA, researchers  have found that gliomas – incurable brain tumors – can arise due to changes in the epigenome, the collection of compounds that are deposited on DNA and alter gene activity without changing the sequence of DNA itself. 

The researchers pinpointed two genes whose activity is epigenetically altered in human gliomas, including one cancer-causing oncogene and one cancer-preventing tumor suppressor gene. 

They show that a PDGFRA insulator and CDKN2A promoter are recurrently methylated in IDH-mutant gliomas.

In animal models, they showed that changes to the epigenome that activate the oncogene and silence the tumor suppressor work in sync to spur brain tumor formation. 

Specifically, disruption of the orthologous insulator in mouse induces PDGFRA and OPC proliferation.

They also developed a mouse glioma model engineered by combining insulator disruption with CDKN2A silencing.

The authors believe that the human-specific features of PDGFRA locus may impact glioma risk and brain development.
 
The findings underscore the potential of therapies that seek to impede gliomas by targeting the epigenome. 

https://www.cell.com/cell/fulltext/S0092-8674(23)00729-8