Brain cancer’s lethal differences: tracking extra DNA

Eunhee Yi, new cancer research, glioblastoma
Postdoctoral Associate Eunhee Yi at The Jackson Laboratory for Genomic medicine. Photo by Jared Skolnick.


The most lethal type of brain cancer, glioblastoma, kills most patients within a few years. Those with the most aggressive cases rarely survive more than one year. There are no effective treatments. There is no long-term survival. The growing glioblastoma tumor increases pressure in the brain, ultimately cutting off blood flow to key parts of the brain, causing death.

Glioblastoma’s deadliness comes from its underlying variability. Glioblastoma tumors differ substantially, both from one tumor to another but also within a single tumor – meaning that there’s no single cure. Variability in the cells that make up the tumor mean that they’re nearly impossible to target, both surgically and chemically. Some glioblastoma cells move throughout the entire brain, making surgical removal impossible. And chemotherapeutics fail when confronted with the diverse cell types that make up the tumor.

has been awarded a $100k fellowship from the American Brain Tumor Association (ABTA) to discover how glioblastoma becomes so aggressive. Yi, a postdoctoral associate working with JAX Professor Roel Verhaak, Ph.D., believes that the differences among individual cells in the tumor are the key to understanding glioblastoma’s resistance. Specifically, Yi studies the genetic differences among glioblastoma cells.

Verhaak’s lab and others have shown that  The role of extra DNA in cancer evolution and therapy resistanceNew research is providing a better understanding of the processes underlying cell-to-cell differences within glioblastoma tumors — a crucial finding because these differences contribute to therapy resistance.glioblastoma cells have extra DNA – segments of the normal chromosomes that have been duplicated over and over and are able to function alongside the normal chromosomes. These extra-chromosomal DNA fragments can contain genes that promote cell growth and division. When there are extra copies of such genes, cells grow and divide too much – the hallmarks of a cancer.

Yi will use the support from the ABTA to discover how the extra-chromosomal DNA is inherited when glioblastoma cells divide. Her research so far indicates that the large variability within glioblastoma tumors may have a lot to do with where the extra-chromosomal DNA goes during cell division: some cells inherit a lot of extra-chromosomal DNA whereas other inherit little or none. Now Yi wants to answer the question of how these differences in the amount of extra-chromosomal DNA affect individual cancer cells.

“If we understand the behavior patterns of extra-chromosomal DNA, we will be able to get a great idea about how can we regulate the intra-tumoral heterogeneity of glioblastoma,” said Yi. She also credits receiving “amazing guidance and support from my mentor, Dr. Roel Verhaak, and JAX’s Sponsored Research team. I am so happy to have been awarded this fellowship from ABTA.”

“We are so incredibly thankful for this strong vote of confidence from the ABTA for the work by Eunhee,” added Verhaak. “With this award, ABTA could not be supporting a more talented researcher. I strongly believe her studies have the potential for critical new insights into the role of extra-chromosomal DNA in glioblastoma cells, and will eventually lead to the development of novel therapeutics for this devastating disease.”

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