Abstract
Background: Liquid biopsy, the analysis of cell-free circulating tumor DNA (ctDNA) in plasma, is becoming an increasingly essential tool in oncology. Current applications for lung cancer include non-invasive analysis of mutations in a tumor with the aim of deciding on therapy, and treatment follow-up, in particular early detection of resistance-causing mutations. Unfortunately the analysis is technically challenging, due to the low amounts of cell-free DNA in plasma and to the minute fraction of tumor-born DNA within it. Current mutation detection methods are either polymerase chain reaction (PCR)-based, allowing highly sensitive detection of a small subset of mutations, or based on high throughput sequencing, which allows screening of broad genomic regions at the expense of sensitivity. A recent technical development, molecular barcodes, brings the sensitivity of sequencing to levels comparable with PCR.
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