Receiving the diagnosis of a brain cancer is undoubtedly disastrous news that nobody wants to hear for themselves or their loved ones. Although significant advances have been made to understand and treat many cancers, the mortality rate remains high for cancers of the brain. New research, however, may be shedding light on one form of brain cancer by investigating the epigenetic character of the disease.
Glioblastoma is the most common and deadliest type of brain cancer in adults. It’s considered a grade IV brain tumor, meaning it replicates very rapidly and is difficult to contain. People between the ages of 50 and 70 are at the highest risk for developing this disease, and those diagnosed typically live for only about a year, at most, even with proper treatment.
Because glioblastoma is very complex and extremely aggressive, it remains elusive to detection and treatment. Generally, tumors develop due to a number of genetic mutations from inherited mutated DNA, or exposure to carcinogens. In addition to the genetic factors, epigenetic modifications to certain genes may also play a role in tumor development.
Epigenetics is the study of heritable modifications in gene expression made without altering the actual DNA sequence, and has been helpful into gaining scientific insight into understanding brain function and mental health as well as treating and preventing cancer,
In a study published in Nature Medicine, scientists from the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences set out to gain elaborate insight on the mechanisms linked to glioblastomas, and how they can develop more effective treatments for this devastating cancer. Specifically, they targeted their focus on DNA and the role that this particular epigenetic mechanism plays in the progression of glioblastoma.
DNA methylation is an epigenetic modification that occurs when a methyl group is added to the 5th cytosine base, forming 5-mC. Methylation to the promoter region of certain genes can silence gene function and as a result can turn off tumor suppressor genes, making this an important area to concentrate on for cancer research.
The research team led by Dr. Christoph Bock utilized reduced representation bisulfite sequencing (RRBS) to measure the DNA methylation levels in brain tissue from over 200 patients with glioblastoma to determine the link between epigenetic modifications and disease progression. They supplemented the data gathered from these patients with digital pathology and brain imaging.
Ph.D. student Johanna Klughammer, a researcher on the study, highlights the importance of examining DNA methylation in cancer research. “DNA methylation sequencing — as a single test — can be used to predict a wide variety of clinically relevant tumor properties, providing us with a powerful new approach for characterizing the heterogeneity of brain tumors,” she said.
They were able to determine a number of different tumor properties at the molecular level, including the differences in DNA methylation levels of primary and reoccurring tumors. They also discovered that fleeting levels of DNA methylation in the microenvironment around the tumor allowed it to renew itself and spread.
Dr. Bock hopes that the methods used in this study can be immediately applied in a clinical approach to create more effective treatment options that extend the life expectancy in patients, “Our study demonstrates what it will take to advance clinical care through biomedical research in Austria: interdisciplinary collaboration, access to the latest technologies, and the ambition and financial resources to successfully perform projects of this scale”.
Source: Christoph Bock et al. (2018) The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space. Nature Medicine 24 1611–1624
Reference: Ce-M-M News “Epigenetic analysis of aggressive brain tumors” Ce-M-M Research Center for Molecular Medicine of the Austrian Academy of Sciences 27 August 2018 Web.