Hypermethylation of Circulating Free DNA in Cutaneous Melanoma

Russell Diefenbach; Jenny Lee; David Chandler; Yinan Wang; Christian Pflueger; Georgina Long; Richard Scolyer; Matteo Carlino; Alexander Menzies; Richard Kefford; Helen Rizos

doi:10.3390/app9235074

Hypermethylation of Circulating Free DNA in Cutaneous Melanoma

Russell Diefenbach, Jenny Lee, David Chandler, Yinan Wang, Christian Pflueger, Georgina Long, Richard Scolyer, Matteo Carlino, Alexander Menzies, Richard Kefford, Helen Rizos

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

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.

Original language	English
Article number	5074
Journal	Applied Sciences
Volume	9
Issue number	23
DOIs	https://doi.org/10.3390/app9235074
Publication status	Published - 1 Dec 2019

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title = "Hypermethylation of Circulating Free DNA in Cutaneous Melanoma",

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.",

author = "Russell Diefenbach and Jenny Lee and David Chandler and Yinan Wang and Christian Pflueger and Georgina Long and Richard Scolyer and Matteo Carlino and Alexander Menzies and Richard Kefford and Helen Rizos",

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T1 - Hypermethylation of Circulating Free DNA in Cutaneous Melanoma

AU - Diefenbach, Russell

AU - Lee, Jenny

AU - Chandler, David

AU - Wang, Yinan

AU - Pflueger, Christian

AU - Long, Georgina

AU - Scolyer, Richard

AU - Carlino, Matteo

AU - Menzies, Alexander

AU - Kefford, Richard

AU - Rizos, Helen

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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ER -

Hypermethylation of Circulating Free DNA in Cutaneous Melanoma

Abstract

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