Precision oncology is predicated upon the ability to detect specific actionable genomic alterations and to monitor their adaptive evolution during treatment to counter resistance. Due to spatial and temporal heterogeneity and co-morbidities associated with obtaining tumor tissues, especially in the case of metastatic disease, traditional methods for tumor sampling are impractical for this application. Known to be present in the blood of cancer patients for decades, cell free DNA (cfDNA) is beginning to inform on tumor genetics, tumor burden and mechanisms of progression and drug resistance. This substrate is amenable for inexpensive non-invasive testing and thus presents a viable approach to serial sampling for screening and monitoring tumor progression. The fragmentation, low yield, and variable admixture of normal DNA present formidable technical challenges for realization of this potential. This review summarizes the history of cfDNA discovery, its' biological properties and explores emerging technologies for clinically relevant sequence-based analysis of cfDNA in cancer patients. Molecular barcoding (or Unique Molecular Identifier, UMI)-based methods currently appear to offer an optimal balance between sensitivity, flexibility and cost and constitute a promising approach for clinically relevant assays for near real time monitoring of treatment-induced mutational adaptations to guide evidence-based precision oncology.
- Received February 9, 2016.
- Revision received June 27, 2016.
- Accepted June 30, 2016.
- Copyright ©2016, American Association for Cancer Research.