New grant funds study of very aggressive childhood brain cancers driven by circular pieces of DNA

Lukas Chavez, Ph.D., has received $3.2 million from the National Institutes of Health to study how unique DNA circles found in cancer cells drive deadly pediatric brain tumors. The research aims to expose how the circular pieces of DNA contribute to therapy resistance and open new therapeutic avenues to improve the lives of people affected by these devastating diseases.

“Our goal for this project is to understand more about the functional relevance of circular extrachromosomal DNA in medulloblastoma, the most common malignant pediatric brain cancer,” says Chavez, assistant professor at Sanford Burnham Prebys. “We hope our findings will lead to a scientific revolution in how some of the most difficult-to-treat childhood brain tumors are understood and treated.”

Extrachromosomal DNA—or ecDNA—was discovered decades ago, but it’s only now, with advanced technology, that researchers can investigate their sequence, structure and regulation. Recent studies have shown that tumor-promoting genes are amplified on ecDNA in some of the most aggressive medulloblastoma tumors, which may contribute to therapy resistance.

The research team has assembled a multi-institutional cohort of Whole Genome Sequencing data from 468 medulloblastoma patient samples. Using novel computational methods for the detection and reconstruction of ecDNA, they will focus on ecDNA in 82 patients (18%) and investigate the link between the presence of ecDNA and significantly poorer outcomes.

“The more we learn about how ecDNA drives pediatric brain tumors—when they form, how they grow and what it might take to stop them—the sooner we can develop novel therapeutic approaches that are urgently needed,” adds Chavez.

The title of the grant, issued by the National Institutes of Health, is “Investigation of ecDNA as a driver of intratumoral heterogeneity and treatment resistance in high-risk medulloblastoma,” Award Number: R01 NS132780-01.