title: Cell-free DNA (cfDNA): Clinical Significance and Utility in Cancer Shaped By Emerging Technologies.
abstract: Precision oncology is predicated upon the ability to detect specific actionable genomic alterations and to monitor their adaptive evolution during treatment to counter resistance. Because of spatial and temporal heterogeneity and comorbidities 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 noninvasive 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. Mol Cancer Res; 14(10); 898-908. ©2016 AACR.
authors.affiliation: Vancouver Prostate Centre, Vancouver, British Columbia, Canada.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Volik
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Miguel
authors.initials: M
authors.lastname: Alcaide
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada. Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada. rmorin@bcgsc.ca ccollins@prostatecentre.com.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Morin
authors.affiliation: Vancouver Prostate Centre, Vancouver, British Columbia, Canada. Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada. rmorin@bcgsc.ca ccollins@prostatecentre.com.
authors.forename: Colin
authors.initials: C
authors.lastname: Collins
mesh_terms: D002474:Cell-Free System; D004273:DNA, Neoplasm / Q000097:blood*; D018450:Disease Progression; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D057285:Precision Medicine
chemical_list: D004273:DNA, Neoplasm