Eunhee Yi, Ph.D.Postdoctoral AssociateThe Jackson Laboratory

Tracing Extrachromosomal DNA Inheritance Patterns in Glioblastoma Using CRISPR Interview with:

Eunhee Yi, Ph.D.Postdoctoral AssociateThe Jackson Laboratory

Dr. Yi

Eunhee Yi, Ph.D.
Postdoctoral Associate
The Jackson Laboratory What is the background for this study? What are the main findings? 

Response: Recurrence after therapy for glioblastoma (GBM) is unavoidable. There are substantial differences among the cells of GBM tumors in the abundance and types of genetic materials. This heterogeneity is a major driver of therapy failure and disease progression. We previously reported that extrachromosomal DNA (ecDNA) elements, which reside outside the linear genome and represent a mechanism to amplify and activate oncogenes, is a potential cause of the increasing genetic diversity in GBM. Our current study is focused on the development of a novel cytogenetic tool to visualize ecDNA to visualize the behavior of these elements in live cells. We have leveraged the unique properties of ecDNA to develop a CRISPR-based “ecDNA tracing toolbox (EDTB)”. What should readers take away from your report? 

Response: Despite the speculation that ecDNA is a key factor of intratumoral heterogeneity, how ecDNA is propagated and distributed among cancer cells is completely unknown. With the tools we are developing, we will be able to answer many questions and uncover unknown biological features such as the generation, distribution, and movement of ecDNA.

This study will significantly improve our understanding of a mechanism that advances cancer evolution and, likely, therapy failure. What recommendations do you have for future research as a result of this work?

Response: We believe ecDNA to be an important aspect of glioma biology, and are speculating that this may also be the case for many other types of cancer. We expect our current research to lead to dramatic new insights into the mechanisms driving ecDNA behavior, with the ultimate goal of developing ecDNA targeting therapeutic modalities that are relevant to a wide variety of cancer patients. Is there anything else you would like to add? 

Response: We are grateful for the support of our work by a Basic Research Fellowship of American Brain Tumor Association, and grants from the B*Cured Foundation, the Musella Foundation and the Brain Tumour Charity. The principal investigator of the work, Roel Verhaak, is a co-founder of and holds equity in Pretzel Therapeutics.


AACR abstract:
Tracing Extrachromosomal DNA Inheritance Patterns in Glioblastoma Using CRISPR 

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Last Updated on April 8, 2019 by Marie Benz MD FAAD