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Volume 9
Issue 23
10.3390/app9235074
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Article

Hypermethylation of Circulating Free DNA in Cutaneous Melanoma

by
Russell J. Diefenbach
1,2,*,
Jenny H. Lee
1,2,
David Chandler
3,
Yinan Wang
3,
Christian Pflueger
4,5,
Georgina V. Long
2,6,7,8,
Richard A. Scolyer
2,6,7,9,
Matteo S. Carlino
2,6,10,
Alexander M. Menzies
2,6,8,
Richard F. Kefford
2,6,11 and
Helen Rizos
1,2
1
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia
2
Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia
3
Australian Genome Research Facility, Victorian Comprehensive Cancer Centre, 305 Grattan St, Melbourne, VIC 3000, Australia
4
Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, Australia
5
Harry Perkins Institute of Medical Research, Nedlands, WA 6009, Australia
6
Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia
7
Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia​
8
Department of Medical Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, NSW 2065, Australia
9
Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, NSW 2050, Australia
10
Crown Princess Mary Cancer Centre, Westmead and Blacktown hospitals, Sydney, NSW 2145, Australia
11
Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia
 
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*
Author to whom correspondence should be addressed.
Appl. Sci. 2019, 9(23), 5074; https://doi.org/10.3390/app9235074
Submission received: 17 August 2019 / Revised: 9 November 2019 / Accepted: 21 November 2019 / Published: 25 November 2019
(This article belongs to the Special Issue Circulating Biomarkers)
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Abstract

Changes in DNA methylation are well documented in cancer development and progression and are typically identified through analyses of genomic DNA. The capability of monitoring tumor-specific methylation changes in circulating tumor DNA (ctDNA) has the potential to improve the sensitivity of ctDNA for the diagnosis and prognosis of solid tumors. In this study we profiled the methylation of seven gene targets (all known to be hypermethylated in metastatic melanoma) within the plasma of patients with advanced melanoma using amplicon-based next generation sequencing of bisulfite-treated DNA. Hypermethylation of 6/7 gene targets, including paraoxonase 3 (PON3) was significantly elevated in patients with metastatic melanoma (n = 4) compared to healthy control samples (n = 5). In addition, the degree of hypermethylation of PON3 and MEOX2 were significantly correlated with ctDNA copy number in melanoma patients, confirming the utility of methylated ctDNA in the absence of tumor mutation data for genes such as BRAF, RAS or EGFR.
Keywords: melanoma; methylation; ctDNA; ddPCR; bisulfite conversion melanoma; methylation; ctDNA; ddPCR; bisulfite conversion

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MDPI and ACS Style

Diefenbach, R.J.; Lee, J.H.; Chandler, D.; Wang, Y.; Pflueger, C.; Long, G.V.; Scolyer, R.A.; Carlino, M.S.; Menzies, A.M.; Kefford, R.F.; et al. Hypermethylation of Circulating Free DNA in Cutaneous Melanoma. Appl. Sci. 2019, 9, 5074. https://doi.org/10.3390/app9235074

AMA Style

Diefenbach RJ, Lee JH, Chandler D, Wang Y, Pflueger C, Long GV, Scolyer RA, Carlino MS, Menzies AM, Kefford RF, et al. Hypermethylation of Circulating Free DNA in Cutaneous Melanoma. Applied Sciences. 2019; 9(23):5074. https://doi.org/10.3390/app9235074

Chicago/Turabian Style

Diefenbach, Russell J., Jenny H. Lee, David Chandler, Yinan Wang, Christian Pflueger, Georgina V. Long, Richard A. Scolyer, Matteo S. Carlino, Alexander M. Menzies, Richard F. Kefford, and et al. 2019. "Hypermethylation of Circulating Free DNA in Cutaneous Melanoma" Applied Sciences 9, no. 23: 5074. https://doi.org/10.3390/app9235074

APA Style

Diefenbach, R. J., Lee, J. H., Chandler, D., Wang, Y., Pflueger, C., Long, G. V., Scolyer, R. A., Carlino, M. S., Menzies, A. M., Kefford, R. F., & Rizos, H. (2019). Hypermethylation of Circulating Free DNA in Cutaneous Melanoma. Applied Sciences, 9(23), 5074. https://doi.org/10.3390/app9235074

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