Cancer assay makes regular monitoring more affordable

Scientists from the National University of Singapore (NUS) have discovered a novel low-cost method of testing for cancers. Called the Heatrich-BS assay, the test sequences clinical samples that have been heated in order to isolate cancer-specific signatures found in a patient’s blood, in a non-invasive alternative to tissue biopsies. It also costs only around S$50 from start to finish, compared to other sequencing methods that can cost up to S$1000 to conduct.

The DNA in our blood, which tells our cells how to synthesise proteins and other important biological building blocks, is produced by different organs in our body. Cancer cells also release DNA into the bloodstream that can be detected by analysing blood samples, known as liquid biopsies. However, sifting through all the genetic material in a sample (whole-genome sequencing) can be expensive and labour-intensive. Some clinicians instead target cancer-specific signatures in cell-free DNA, almost like hunting for specific faces in a large crowd of people instead of inspecting every single individual; yet even these methods can be imperfect.

“Some patients may have cancer signatures that look slightly different and allow them to slip through the screening process,” noted Assistant Professor Cheow Lih Feng from NUS. Cheow’s team has now discovered a way to discard the non-informative sections in a patient’s DNA to target where most cancer-specific biomarkers are concentrated.

Our DNA is made up of molecules known as nucleotides: adenine (A), thymine (T), guanine (G) and cytosine (C). Cancer-specific signatures tend to be concentrated in areas of the genome that have high repetitions of C and G nucleotides, known as CpG islands, that make up only around 1% of our genome.

“We were performing some unrelated experiments, and one of our researchers heated a sample,” Cheow said, recounting the team’s accidental discovery that heat destroyed non-informative sections of the genome but left CpG islands largely intact. This allowed them to sequence the remaining genome and detect the presence of cancers for a minute fraction of the average market price.

“We are getting a much more sensitive assay at almost the same costs as compared to simple protein biomarker tests,” Cheow said. “Our method really concentrates on sequencing these regions that matter the most.”

The assay was trialled at Singapore’s National Cancer Centre, monitoring patients with colorectal cancer. By comparing the results of their blood analysis with CT scans that imaged the size of patients’ tumours, the team found that there was a high correlation between how much cancer-specific DNA was detected in a patient’s blood sample and the size of their tumours over time. “This way, doctors can monitor patients for their response to treatment and tailor their therapy regimes,” Cheow said.

He added that the method has the potential to work universally across all types of cancer since they all demonstrate the property of enriching CpG islands with cancer-specific biomarkers. The assay may also help accelerate future research, helping scientists study different subtypes of cancer for a low cost and therefore improving the development of future cancer diagnoses and therapies.

The NUS team have published their findings in the journal Science Advances and filed a patent for their discovery. They are now looking to partner with pharmaceutical and biotechnology companies that can help bring the assay to market.

Image caption: Assistant Professor Cheow Lih Feng (right), his former PhD student Dr Elsie Cheruba (left) and their team have developed the Heatrich-BS assay. Image credit: NUS Institute for Health Innovation & Technology.

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