American Journal of Clinical Dermatology

, Volume 20, Issue 1, pp 1–12 | Cite as

Monitoring Melanoma Using Circulating Free DNA

  • Russell J. DiefenbachEmail author
  • Jenny H. Lee
  • Helen Rizos
Leading Article


Genetic material derived from tumours is constantly shed into the circulation of cancer patients both in the form of circulating free nucleic acids and within circulating cells or extracellular vesicles. Monitoring cancer-specific genomic alterations, particularly mutant allele frequencies, in circulating nucleic acids allows for a non-invasive liquid biopsy for detecting residual disease and response to therapy. The advent of molecular targeted treatments and immunotherapies with increasing effectiveness requires corresponding effective molecular biology methods for the detection of biomarkers such as circulating nucleic acid to monitor and ultimately personalise therapy. The use of polymerase chain reaction (PCR)-based methods, such as droplet digital PCR, allows for a very sensitive analysis of circulating tumour DNA, but typically only a limited number of gene mutations can be detected in parallel. In contrast, next-generation sequencing allows for parallel analysis of multiple mutations in many genes. The development of targeted next-generation sequencing cancer gene panels optimised for the detection of circulating free DNA now provides both the flexibility of multiple mutation analysis coupled with a sensitivity that approaches or even matches droplet digital PCR. In this review, we discuss the advantages and disadvantages of these current molecular technologies in conjunction with how this field is evolving in the context of melanoma diagnosis, prognosis, and monitoring of response to therapy.


Compliance with Ethical Standards


Russell J. Diefenbach was supported in part by a donation to Melanoma Institute Australia from the Clearbridge Foundation. This work was also supported in part by the National Health and Medical Research Council (APP1093017 and APP1128951). Helen Rizos is supported by a National Health and Medical Research Council Research Fellowship.

Conflict of interest

Russell J. Diefenbach, Jenny H. Lee, and Helen Rizos declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Biomedical Sciences, Faculty of Medicine and Health SciencesMacquarie UniversitySydneyAustralia
  2. 2.Melanoma Institute AustraliaSydneyAustralia

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