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A study of prostate cancer evolution during metastasis observes that liquid biopsies do not capture the complete genetic diversity of the disease within a patient.

Prostate cancer affects 48,500 men in the UK every year [Cancer Research UK] and is frequently driven by changes in the DNA that occur during a person’s lifetime. However, even after cancer initiation, individual tumour cells continue to evolve by accumulating DNA changes, leading to genetic variation between cells even within the same tumour. In addition, some of these prostate cancer cells can spread or ‘metastasise’ to other parts of the body, which can lead to multiple tumours with different underlying DNA changes. Since the genetic make-up of the tumour(s) can influence the choice of therapy, it is important to accurately assess this genetic diversity in prostate cancer patients.

DNA sequencing technology is becoming more readily available in the clinic, which can enable genetic testing. However, one challenge is that tissue biopsies are unlikely to sample the full range of genetic variation within different regions of a tumour or associated metastatic tumours. One solution may be to take liquid biopsies and analyse the tumour DNA that circulates in the blood or other bodily fluids, which may be able to better sample the full genetic variation of the cancer in the body.

Dr Dan Woodcock and colleagues from the Big Data Institute, Oxford and Tampere University, Finland, have studied the DNA sequences from different regions within the primary prostate and metastatic tumours, and compared these to those identified from six different types of liquid biopsies. Published in the journal Nature Communications, their research identified that blood-based liquid biopsies were able to capture much of the genetic variation in the metastases but that some genetic alterations were not represented, most notably those that were only observed in the primary prostate tumour. Further, they found that certain DNA mutations were detected in the cerebrospinal fluid but not the blood and vice versa, indicating that perhaps a combination of different types of liquid biopsies might be beneficial for measuring the full genetic diversity to inform treatment choice.

Liquid biopsies have great promise for the earlier detection of cancer and for monitoring of cancer recurrence. The results of this study highlight how sequencing of DNA from liquid biopsies can detect cancer but may not fully represent its genetic diversity, especially if it has already metastasised, which has implications for how liquid biopsies are used in the future in the clinic.