Advantages of circulating tumor DNA

Tissue:  the inconvenient "gold standard"

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.

Advantages of blood-based testing

  • ctDNA provides real-time information about the current mutational status of the tumor
  • Non-invasive liquid biopsies minimize cost and risk to patients
  • Easily performed in situations where no tumor tissue is available or accessible
  • Systemic approach assesses the mutational status of the tumor eliminating the selection bias inherent with tissue samples
  • For a concrete example of how circulating tumor DNA testing can be utilized in clinical practice, we put together a resource using anti-EGFR resistance in non-small cell lung cancer (NSCLC) to illustrate the clinical utility of OncoBEAM digital PCR technology for detecting ctDNA. You can access this resource here: Sysmex OncoBEAM circulating tumor DNA testing in clinical practice.


The Sysmex Inostics approach

Learn more about our SafeSEQ panels for your blood-based testing needs including specific genes for disease-specific coverage, data from SafeSEQ’s remarkably high precision and accuracy, and close concordance with our enhanced digital PCR OncoBEAM technology offering.





Detect a much higher percentage of your intended-use population by using disease-specific panels that offer both high sensitivity and specificity, in contrast to ‘pan cancer’ panels currently available.


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

6. Schwarzenbach H, Stoehlmacher J, Pantel K,et al: Detection and monitoring of cell-free DNA in blood of patients with colorectal cancer. Ann N Y Acad Sci 1137:190-196, 2008
7. Fleischhacker M, Schmidt B: Circulating nucleic acids (CNAs) and cancer: A survey. Biochim Biophys Acta 1775:181-232, 2007
8. Diaz, L. A. Jr et al. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 486, 537–540 (2012).
9. Misale, S. et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature 486, 532–536 (2012).