In contrast to previous tests which sequenced circulating tumour DNA (ctDNA) shed into the bloodstream by tumour cells, the new assay covers 508 genes -- 'almost ten times more of the genome than any other previously reported cell-free DNA assays at these sequencing depths,' said Dr Pedram Razavi, lead study author and medical oncologist at Memorial Sloan Kettering Cancer Center in the USA.
This enhanced coverage of the genome is important as even tumours of the same cancer type can carry mutations in different genes. 'The more of the genome that you cover, the higher the chances of finding mutations that come from the tumour,' Dr Razavi added.
Fragments of tumour DNA in the blood can be detected by a number of commercial tests to aid monitoring of cancer development in already-diagnosed patients. This study aimed to remove the need for biopsies from the tumours themselves, paving the way for earlier cancer detection.
The test used a high-intensity sequencing approach, covering almost two million bases of DNA. Each region of the genome was 'read' 60,000 times, creating a highly sensitive assay for a large portion of the genome.
The team collected blood from 124 patients diagnosed with metastatic breast, non-small cell lung, and prostate cancer. They isolated and sequenced ctDNA, along with DNA from the patient’s white blood cells. This control step allowed them to identify cancer-derived mutations in the ctDNA.
The group then compared these blood assay mutations with those identified in tumour tissue biopsies from the same patients. Of 864 mutations identified in tumour biopsies, 627 (73 percent) were found present in the bloodstream. In 89 percent of patients, at least one of the mutations identified in the tumour tissue was also found in the blood.
'The ability of this assay to detect ctDNA without prior knowledge of tumour sequencing results and with an unprecedented breadth of signals are both important findings that support the possible feasibility of applying this approach to detection of cancer at earlier stages,' said Dr Razavi.
'We continue to see promising reports about possible uses of circulating tumour DNA analysis. While this approach has a ways to go before it becomes a proven technology for early cancer detection, this research is an important step in that direction,' said Dr John Heymach, an expert at the American Society of Clinical Oncology (ASCO).