Summary
A 12-patient preprint reports that duplex sequencing detected the aristolochic acid-associated SBS22a mutation signature in blood and urine from patients with signature-positive urothelial tumours. The findings are a proof of concept, not yet a validated population screening test.
A medRxiv preprint reports that duplex sequencing of blood and urine samples detected SBS22a, a DNA mutation pattern associated with aristolochic acid exposure, in patients whose urothelial tumours carried the same signature. The study involved 12 patients with urothelial carcinoma and presents the approach as a proof of concept for detecting exposure-related mutations without relying on tumour tissue.
Aristolochic acids are compounds found in some herbal remedies. They can damage the kidneys and cause cancer. Current genomic detection of past exposure typically relies on sequencing a tumour after it has formed. The researchers instead looked for non-clonal mutations—mutations associated with exposure but not sought as part of an established tumour’s expanded cell population.
How the test was studied
The team analysed matched tumour and normal tissues alongside peripheral blood, urine sediments and sorted immune-cell fractions. Duplex sequencing is an error-correcting method that reads both strands of DNA, helping distinguish genuine, rare mutations from sequencing errors. The researchers also used single-cell whole-genome sequencing to investigate which immune cells carried the signal.
In the patient cohort, the researchers reported recovering the canonical aristolochic acid signature, SBS22a, in blood and urine from patients with AA-positive tumours; they did not find it in samples from patients with AA-negative tumours. Analysis of immune-cell fractions localised the signal to adaptive lymphocytes, which the authors describe as long-lived cells that can retain a record of past mutational exposure.
Why the result is a proof of concept
The finding suggests that exposure-related mutations may be detectable in accessible samples, potentially enabling research into risk assessment before a tumour forms. But the study tested a small group of people who already had urothelial cancer. Establishing whether the method can identify exposure reliably in people without cancer—and how it might be used for population-level risk assessment—will require further evaluation.
The report is a preprint, so its findings have not yet completed peer review. Its disclosures state that four authors were employees of and equity holders in TwinStrand Biosciences at the time of the work.