Epigenetic Modifications Drive Brain Cancer

Scientists have identified an epigenetic modification that controls the aggressiveness of glioblastoma stem cells.

AsianScientist (Oct. 15, 2014) – Scientists from the University of Tokyo have identified an epigenetic modification which may be responsible for the aggressive brain tumor, glioblastoma. Their results have been published in Cell Reports.

Glioblastoma is one of the most malignant forms of cancer; patients with the disease have a mean survival rate of only one year. Increasing evidence points to cancer stem cells as the drivers of the disease, a small fraction of cells that reside deep within the tumor and are resistant to conventional therapeutics.

In the present study, researchers including Professor Tetsu Akiyama and his Ph.D. student Hiroki Takai investigate the role of epigenetic modifications on the ability of cancer stem cells to drive tumor formation.

Obtaining samples from glioblastoma patients, they maintained the cells in serum-free medium, a method which enriches for glioblastoma stem cells. When they analyzed the cells’ DNA, they found that the glioblastoma cells had elevated levels of an epigenetic modification called hydroxymethylated cytosine (5hmC). Furthermore, they showed that 5hmC modification played a critical role in the ability of the glioblastoma cells to form tumors.

In subsequent experiments, the researchers found that 5hmC enriched genes recruit genetic machinery which cause structural changes in the DNA, thereby increasing the transcription of cancer-related genes.

These findings provide insight into the molecular mechanisms underlying the tumorigenicity of glioblastoma. Moreover, these findings raise the possibility that enzymes involved in hydroxymethylation of DNA could be promising molecular targets for glioblastoma therapy. Since mice deficient for these enzymes are viable, compounds targeting these enzymes are expected to have limited side effects.

The article can be found at: Takai et al. (2014) 5-Hydroxymethylcytosine Plays a Critical Role in Glioblastomagenesis by Recruiting the CHTOP-Methylosome Complex.


Source: University of Tokyo.
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