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Although genomic analysis using tissue specimens (fresh, fresh-frozen, or formalin-fixed/ paraffin embedded) is the current gold-standard for molecular oncology, tissue analysis can have considerable drawbacks.
Invasive tissue biopsy can significantly increase the cost of patient care, and comes with the inconveniences and risks associated with surgical procedures (1) . False results can also occur as a result of tumor heterogeneity, where cells captured by the local tissue biopsy are not representative of the genomic diversity across all malignant cells. Tissue can also be difficult to obtain in sufficient quantities, and repeat biopsy across sequential timepoints is not practical (2-3).
It is now well established that tumor cells shed small DNA fragments into the circulation, with most of these fragments being compartmentalized in the plasma component of whole blood (4-7).
The amount of detectable tumor-derived cell-free DNA has been shown to correlate with tumor burden, and can dynamically change in response to treatment or surgery. Importantly, circulating tumor DNA can be a source of genomic material originating from subpopulations of tumor cells that are resistant to treatment and can drive disease progression (8, 9). Because it has the potential to overcome the biological and clinical challenges associated with tissue biopsy, ctDNA analysis continues to advance towards routine clinical practice.
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1. Overman MJ, Modak J, Kopetz S, et al: Use of research biopsies in clinical trials: Are risks and benefits adequately discussed? J Clin Oncol 31:17-22, 2013
2. Vogelstein B, Papadopoulos N, Velculescu VE, et al: Cancer genome landscapes. Science 339:1546-1558, 2013
3. Gerlinger M, Rowan AJ, Horswell S, et al: Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366:883-892, 2012
4. Hashad D, Sorour A, Ghazal A, et al: Free circulating tumor DNA as a diagnostic marker for breast cancer. J Clin Lab Anal 26:467-472, 2012
5. Salvianti F, Pinzani P, Verderio P, et al: Multiparametric analysis of cell-free DNA in melanoma patients. PLoS One 7:e49843, 2012