A new study led by the Bernstein Laboratory at Dana-Farber and the Broad Institute of MIT and Harvard showed that the formation of gliomas—deadly brain tumors—can be driven by alterations in the epigenome. These changes occur without any variation in the DNA sequence itself. This discovery, recently published in the journal Cell, challenges the prevailing understanding that cancers primarily arise from DNA mutations.
Contrary to the common belief that cancers primarily emerge from mutations in the DNA sequence, this study suggests that gliomas can also originate due to modifications in the epigenome, the compounds that influence DNA activity without altering its sequence. The researchers have identified two genes that undergo epigenetic changes in human gliomas: an oncogene that promotes cancer growth and a tumor suppressor gene that inhibits it.
The team also conducted studies on animal models which reinforced their findings. Their experiments revealed that simultaneous changes in the epigenome, specifically the activation of the oncogene and the silencing of the tumor suppressor gene, are crucial for triggering brain tumor development.
The focus of their study was a CTCF insulator, a regulatory element near the PDGFRA oncogene, recurrently disrupted by methylation in gliomas. Their research illustrates the tumorigenic capacity of recurrent epigenetic lesions, particularly those involving the disruption of insulators and silencing of the tumor suppressor gene.
These findings significantly expand our understanding of the genesis of gliomas and highlight the potential of developing therapies that target the epigenome to inhibit tumor growth. The discovery that glioma brain tumors can be driven by epigenetic changes suggests that new chemotherapy agents specifically targeting these alterations may be key to halting tumor progression.
Contrary to the common belief that cancers primarily emerge from mutations in the DNA sequence, this study suggests that gliomas can also originate due to modifications in the epigenome, the compounds that influence DNA activity without altering its sequence. The researchers have identified two genes that undergo epigenetic changes in human gliomas: an oncogene that promotes cancer growth and a tumor suppressor gene that inhibits it.
The team also conducted studies on animal models which reinforced their findings. Their experiments revealed that simultaneous changes in the epigenome, specifically the activation of the oncogene and the silencing of the tumor suppressor gene, are crucial for triggering brain tumor development.
The focus of their study was a CTCF insulator, a regulatory element near the PDGFRA oncogene, recurrently disrupted by methylation in gliomas. Their research illustrates the tumorigenic capacity of recurrent epigenetic lesions, particularly those involving the disruption of insulators and silencing of the tumor suppressor gene.
These findings significantly expand our understanding of the genesis of gliomas and highlight the potential of developing therapies that target the epigenome to inhibit tumor growth. The discovery that glioma brain tumors can be driven by epigenetic changes suggests that new chemotherapy agents specifically targeting these alterations may be key to halting tumor progression.