Dartmouth Researchers Link DNA Defect to Survival Rate from Deadly Brain Cancer, Glioblastoma

In their scientific paper published on Nature, entitled 5-Hydroxymethylcytosine Localizes to Enhancer Elements and Is Associated with Survival in Glioblastoma Patients, researchers from Dartmouth's Norris Cotton Cancer Center (NCCC) makes a breakthrough discovery, identifying the functional role of two specific DNA modifications in glioblastoma (GBM) tissues.

The American Brain Tumors Association defines glioblastoma as tumors from astrocytes, the star-shaped cells that make up the "glue-like," or supportive tissue of the brain. These tumors are largely found inside the cerebral hemispheres of the brain, but can also occur anywhere in the brain or spinal cord. Although rare, glioblastoma are almost always diagnosed as malignant (cancerous), because the cells reproduce quickly and they are supported by a large network of blood vessels.

The researchers spearheaded by Cancer Center Member, Brock Christensen, PhD, Associate Professor of Epidemiology at Dartmouth's Geisel School of Medicine, analyzed the profile of multiple DNA modifications, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5-hmC), in a set of 30 glioblastomas in collaboration with clinicians at NCCC.

"An intense interest has emerged in detailing the functional role of distinct DNA modifications in both healthy and disease tissues," Christensen told Eureka Alert .

"Here, we uncovered that specific DNA 5mC and 5hmC patterns are disrupted in GBM and uniquely characterize the molecular switches of the genome known as 'enhancers.' Importantly, we discovered that 5hmC signatures had a particularly strong association with patient survival."

Unlike past studies that, due to technical limitations, were unable to explore the high-resolution 5mC and 5hmC levels in a cancer genome at the same time, the Dartmouth study, through the use of advanced molecular biology and statistical approaches -including the Dartmouth Discovery Computing Cluster and Nano String nCounter technology - successfully identified the levels of the distinct DNA modifications across the critical regions of the genome.

"Together, our work reveals more about the powerful influence of the epigenome in cancer and highlights the distinct functional role of 5hmC," explains Christensen.