Researchers from the Francis Crick Institute and UCL have used data held in the National Genomic Research Library to show that rogue genetic material called extrachromosomal DNA (ecDNA) can drive the survival of some of the most aggressive cancers.

These circular fragments of DNA can increase tumour spread, boost the activity of cancer-driving genes and block the immune system from fighting back.

The new research is published in Nature, from the Cancer Research UK and NCI-funded eDyNAmiC Cancer Grand Challenges team, showing that ecDNA is linked to shorter patient survival and could represent a new treatment target.

Our DNA is usually stored within structures called chromosomes but, in cancer, tiny circles of rogue genetic material called ecDNA can exist outside of the chromosome. These runaway particles carry important cancer-driving genes and don’t follow the same rules as chromosomal DNA, allowing cancer cells to adapt quickly, evade treatments and grow uncontrollably.

Using data from the 100,000 Genomes Project housed in the National Genomic Research Library, the research team analysed whole genome sequence data from nearly 15,000 patients with cancer across 39 tumour types. They found that over 17% of the samples contained ecDNA, with the highest rates seen in sarcomas, glioblastoma and a type of breast cancer.

By profiling ecDNA genes, they found that many functioned to promote cancer-driving genes, and others modified the immune system by depleting immune T cells that would normally attack a tumour.

The researchers hope that identifying and targeting vulnerabilities in ecDNA could stop tumours from evolving and becoming resistant to treatment.

Genomics England thanks the participants who consented to donate their data for the 100,00 Genomes Project that made this research and its findings possible.

“This research demonstrates the value of large genomic datasets like the National Genomic Research Library, and how they can provide vital information that make new discoveries in cancer or rare conditions possible.

“These findings will be a valuable asset in helping researchers around the world to make even more advances in how we understand and potentially treat cancer through more targeted therapies that patients respond best to.”

Professor Matt Brown

Chief Scientific Officer at Genomics England

“These rogue pieces of DNA create even more genetic variation within a tumour, something that we know is associated with cancer spread and resistance to treatment.

“If we could target ecDNA specifically, we might be able to boost response to standard cancer therapies. Our work has opened up new questions, such as how ecDNA forms in the first place, and when would be best to target it.”

Chris Bailey

first author and clinician scientist at the Crick and University College London Hospital

“Our understanding of ecDNA is a step forward in building a complete picture of the complex biology of cancer. These circles of rogue DNA are a unique way for the tumour to hide from the immune system and evolve resistance to treatment.   

“Now that we’ve now identified tumour types more likely to have ecDNA, we can work to target the ecDNA, with the aim of trying to improve response to cancer therapies.”

Charles Swanton

Deputy Clinical Director and Head of the Cancer Evolution and Genome Instability Laboratory at the Crick and senior author of the study

Cancer