Illustration of a read out from a Sanger sequencer to demonstrate the power of genomic screening for identifying inherited conditions at an early stage.
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Oxford Nanopore Technologies and Dutch start-up Cyclomics have announced “developer access” to a new research workflow they call “the world’s first nanopore sequencing-based solution for ultra-sensitive detection of circulating tumor DNA (ctDNA).”

The system works by detecting and analyzing cell-free DNA (cfDNA) in the blood stream. As tumor cells die, they release DNA. Specific mutations in those tumor cells can be found in the ctDNA. But the detection of ctDNA has historically been challenging, as a very low percentage of the cfDNA in the blood typically originates from the tumor.

“Monitoring recurring cancer today involves time-consuming, invasive scans and tests— many of which are expensive and stressful. We are proud to introduce a new method that could signal a paradigm shift in cancer detection and management by enabling healthcare providers to detect recurring cancer, with nearly 100% accuracy in the case of TP53 in the Cyclomics study, through only a blood draw,” said Gordon Sanghera, CEO, Oxford Nanopore Technologies.

CyclomicsSeq is a novel ctDNA and cfDNA detection and analysis method that leverages nanopore technology to deliver fast and low-cost sequencing with the potential to be deployed at the point of care. The company says individual ctDNA molecules present in blood can be sequenced—with near 100% accuracy for TP53 as shown in a recent clinical study—allowing for indirect detection of a specific tumor from a blood draw.

In a proof-of-concept study published in NPJ Genomic Medicine, the team demonstrated that a CyclomicsSeq assay for TP53 could be used to successfully monitor tumor burden during treatment for head-and-neck cancer patients. They were able to facilitate the detection of mutations at frequencies down to 0.02% and the entire workflow took around three days—significantly less than current approaches to detect mutations in ctDNA.

CyclomicsSeq uses nanopore technology’s to target the ctDNA and cfDNA in the 200base pair range. CyclomicsSeq can also be used on any Oxford Nanopore device, therefore no new equipment is necessary to perform highly accurate analyses.

Oxford Nanopore and Cyclomics entered a multi-year research collaboration and licensing agreement to fine-tune the method with the goal of enabling robust detection of rare mutations that are present at below 0.5% in cfDNA. Further optimizations, including the detection of methylation—which provides critical information on cancer and can be elucidated in real time using nanopore sequencing—are now underway.

A first universal version of the CyclomicsSeq workflow, which includes library prep and analysis, is now in trial with select users in a developer access program. The companies say an open early access program will follow in the coming months.

The companies are also initiating multiple clinical research studies, including with Erasmus Medical Center in The Netherlands and other institutions to assess the clinical utility of their sequencing solution, including the clinical benefit of quick turnaround gained by not having to wait to batch samples.

Bianca Mostert, Oncologist at Erasmus Medical Center, said, “Accurate low frequency variant calling from cfDNA has the potential to improve on current clinical response evaluation after neoadjuvant chemoradiation in oesophageal cancer. CyclomicsSeq offers a very promising solution for this purpose and we are looking forward to evaluating it”.

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