Researchers at Weill Cornell Medicine and the New York Genome Center have developed a new method for early cancer detection using whole-genome sequencing of DNA.
The new error-correction technique has shown higher sensitivity and accuracy than previous methods and represents a significant advancement towards routine blood test-based cancer screening.
The study, recently published, evaluated the cancer-detection performance of a new commercial sequencing platform from Ultima Genomics.
Its lower cost allows for a high depth of coverage, a crucial measure of sequencing data quality, enabling the detection of low concentrations of circulating tumour DNA.
The integration of an error-correcting method further enhanced the accuracy of the technique.
Weill Cornell Medicine’s Englander Institute for Precision Medicine and the Sandra and Edward Meyer Cancer Center member and New York Genome Center core faculty member Dan Landau said: “We’re now entering an era of low-cost DNA sequencing, and in this study, we took advantage of that to apply whole-genome sequencing techniques that in the past would have been considered wildly impractical.
“These results allow us to think about a future in which we can detect and track cancer from blood tests alone.”
For nearly a decade, the Landau laboratory has been addressing challenges in blood-test-based liquid biopsy technology for early cancer detection.
Unlike methods focusing solely on targeted DNA sequences, the researchers employed whole-genome sequencing, which does not require prior knowledge of mutation locations.
Building on last year’s study, which detected advanced melanoma and lung cancers from blood samples without tumour sequence data, the new research took the approach further.
The new study allowed for a depth of whole-genome sequencing previously not feasible due to high cost, enabling tumour DNA detection in blood samples at part per million concentrations.
The team improved the method’s accuracy by implementing an error-correction technique that utilises the redundant information in natural two-stranded DNA.
This advancement results in extremely low error rates, making it feasible to use blood samples without needing patient tumour data.
The researchers showed the method’s potential by detecting and assessing very low cancer levels in patients with bladder cancer and melanoma using blood samples alone.
The research was partly supported by the National Cancer Institute, the Mark Foundation Aspire Award, the Burroughs Wellcome Fund Career Award for Medical Scientists, and the Melanoma Research Alliance Established Investigator Award.
Englander Institute for Precision Medicine chief research officer and Weill Cornell Medicine associate professor of medicine and of cell and developmental biology Bishoy Faltas said: “This collaboration allowed us to analyse circulating tumour DNA from patients with bladder cancer and identify the distinct mutational signatures that my lab has extensively studied.
“Incorporating these signatures into the analysis significantly increased the sensitivity of circulating tumour DNA detection.”
The study’s first author Alexandre Cheng said: “We were able, for example, to see increases in circulating tumour DNA levels after treatment in patients with cancers that progressed or recurred, and declines in those levels in patients whose cancers had full or partial responses.”
