In a world-first, the team were able to detect the DNA barcodes shed by the primary tumour in plasma samples.
GLOBAL: Australian scientists have discovered that DNA barcoding can be used to track cancer cells in solid and liquid biopsies, empowering future research into more reliable breast cancer diagnosis and treatment strategies.
Tumours are composed of different cancer cells that vary in their aggressiveness and sensitivity to treatments, and further research is needed to understand how solid biopsies (from the tumour), or liquid biopsies (from the blood), can capture this diversity.
DNA barcoding technology is a powerful tool to study cancer heterogeneity using lentiviruses to label individual cancer cells with DNA tags. These tags act as barcodes, which can then be tracked and identified in tumour cells and matched biopsies.
Using an optimised DNA barcoding technique, researchers at the Olivia Newton-John Cancer Research Institute (ONJCRI), WEHI and Peter MacCallum Cancer Centre found that tumours in different models shed different amounts of DNA into the bloodstream, even when their cancer cell makeup looks similar.
In a world-first, the team were able to detect the DNA barcodes shed by the primary tumour in blood and plasma samples.
The discovery that DNA tag detectability varies across models, with some showing low recovery even when highly metastatic, indicates that DNA shedding is model-specific and could contribute to false-negative liquid biopsy results.
Dr Antonin Serrano, who undertook the research at ONJCRI and WEHI and is now a Postdoctoral Researcher at the University of Melbourne, shares the key findings from this research:
“DNA barcoding enabled us to investigate entire tumours, solid biopsies and even liquid biopsies. We were then able to accurately quantify how much tumour heterogeneity is captured in biopsies.
“We found that DNA shedding in the bloodstream varied widely, not only depending on necrosis and tumour burden, but also across preclinical models.
“We also found that barcode diversity in the centre of primary tumours was significantly higher than in the periphery, which could have significant implications for the interpretation of solid biopsies.”
Prof Delphine Merino, Laboratory Head at ONJCRI and senior author of the Molecular Systems Biology paper published today, says:
“Our results suggest that both liquid and solid biopsies are, overall, representative of tumour composition, but the results vary between tumours, suggesting that combining both strategies may provide a more accurate representation of the disease.”
Co-senior author and breast cancer clinician Prof Sarah-Jane Dawson, Peter MacCallum Cancer Centre, says:
“Liquid biopsies are a non-invasive way to monitor disease progression. This research will help us understand why some tumours are shedding more DNA than others, and could ultimately lead to a better use of liquid biopsies in the clinic.”
In 2025, there were 20,336 new cases of breast cancer diagnosed in Australia, with an estimated 3,353 deaths.
Dr Tom Weber (WEHI) is a co-first author, and Prof Shalin Naik (WEHI) is a co-senior author of the Molecular Systems Biology paper.
This work was supported by Love Your Sister, National Health and Medical Research Council (NHMRC) and the National Breast Cancer Foundation.
ENDS
Publication available at: https://link.springer.com/article/10.1038/s44320-026-00194-w
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About the Olivia Newton-John Cancer Research Institute (ONJCRI)
ONJCRI is a global leader in advancing cancer research, driven by the singular goal of improving patient outcomes. We drive progress by discovering and developing diagnostics and therapeutics that are more effective, tolerable, and accessible. ONJCRI adopts a tumour-agnostic approach, targeting shared pathways across multiple cancer types. This innovative strategy enables us to deliver scalable and impactful therapies that benefit diverse patient populations, accelerating progress across the entire landscape.
By bridging laboratory discoveries and clinical applications, ONJCRI is redefining how cancer treatments are designed and delivered: from bedside to bench to bedside. With a steadfast commitment to equity, innovation, and collaboration, we strive to transform cancer care, addressing unmet needs and overcoming disparities in access for all communities. For more about the Olivia Newton-John Cancer Research Institute, visit www.onjcri.org.au.
ONJCRI is an independent medical research institute and is affiliated with La Trobe University as the School of Cancer Medicine.