A recent paper published in JAMA Oncology by Torga & Pienta revealed that, strikingly, 2 major commercial liquid biopsy tests show significant and clinically unacceptable discordance.
Why do liquid biopsy tests differ so significantly? Are they reliable?
Among other impact factors, the extraction method of circulating free DNA (cfDNA) plays a major role here. Data show that different cfDNA extraction methods yield significantly different amounts of cfDNA by 10% to 10 folds, and consequently result in discordant conclusions. When we study genomic DNA isolated from the nucleus of cells, this level of difference may not matter much – because the amount of genetic material commonly reaches hundreds of micrograms (ug), so the downstream testing methods have enough genetic material to work with anyway. However, when we study cfDNA, this level of difference may result in a fundamental discordance, because the amount of cfDNA is commonly less than 100 nanograms (ng). Slight difference of cfDNA yields may result in critical impact on the testable copies of cancer mutations and the signal-to-noise ratio.
We illustrate how the accuracy of a liquid biopsy is impacted by the cfDNA sample preparation in a figure below. To have a reliable liquid biopsy testing, a highly efficient cfDNA extraction must be achieved.
Exhibit 1. Sample preparation is a critical yet unaddressed challenge in liquid biopsy.