Liquid Biopsy in Tumor Genetic Diagnosis

Liquid biopsy involves the analysis of cell-free nucleic acids, mainly circulating free DNA (cfDNA), in bodily fluids such as blood. The obtaining of specimens is easier for patients and less invasive than tissue biopsy, but the method has certain limitations.

This review is based on pertinent publications retrieved by a selective literature search.

Because the concentration of cfDNA in plasma is less than 0.001%, special amplifying techniques must be used to enable a search for specific mutations. Liquid biopsy can be used in patients with non-small cell lung cancer (NSCLC) if no tissue is available for biopsy; when performed for this indication, it has 67% sensitivity and 94% specificity. If liquid biopsy does not reveal a mutation, this may be due either to the absence of the mutation in the tumor or to the inadequate sensitivity of the measuring technique. This uncertainty associated with negative findings can be reduced by the simultaneous demonstration of reference mutations derived from a primary tumor tissue analysis. In comparison to tissue studies, the search for tumor-specific mutations by liquid biopsy is 70% sensitive and 69% specific; this corresponds to a positive predictive value of 86% and a negative predictive value of 46%.

Liquid biopsy and tumor tissue analysis are complementary, rather than alternative, techniques for therapeutically relevant genetic investigation of tumors. Comparative studies are needed so that further indications can be determined for liquid biopsy in the diagnostic evaluation of cancer.