Hypermethylation of circulating free DNA in cutaneous melanoma

Russell J. Diefenbach; Jenny H. Lee; David Chandler; Yinan Wang; Christian Pflueger; Georgina V. Long; Richard A. Scolyer; Matteo S. Carlino; Alexander M. Menzies; Richard F. Kefford; Helen Rizos

doi:10.3390/app9235074

Hypermethylation of circulating free DNA in cutaneous melanoma

Russell J. Diefenbach, Jenny H. Lee, David Chandler, Yinan Wang, Christian Pflueger, Georgina V. Long, Richard A. Scolyer, Matteo S. Carlino, Alexander M. Menzies, Richard F. Kefford, Helen Rizos

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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.

Original language	English
Article number	5074
Pages (from-to)	1-17
Number of pages	17
Journal	Applied Sciences
Volume	9
Issue number	23
DOIs	https://doi.org/10.3390/app9235074
Publication status	Published - 25 Nov 2019

Bibliographical note

Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

Melanoma
methylation
CtDNA
ddPCR
bisulfite conversion

Access to Document

10.3390/app9235074

Publisher version (open access)Final published version, 1.3 MBLicence: CC BY

Cite this

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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.",

keywords = "Melanoma, methylation, CtDNA, ddPCR, bisulfite conversion",

author = "Diefenbach, \{Russell J.\} and Lee, \{Jenny H.\} and David Chandler and Yinan Wang and Christian Pflueger and Long, \{Georgina V.\} and Scolyer, \{Richard A.\} and Carlino, \{Matteo S.\} and Menzies, \{Alexander M.\} and Kefford, \{Richard F.\} and Helen Rizos",

note = "Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2019",

month = nov,

day = "25",

doi = "10.3390/app9235074",

language = "English",

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journal = "Applied Sciences",

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TY - JOUR

T1 - Hypermethylation of circulating free DNA in cutaneous melanoma

AU - Diefenbach, Russell J.

AU - Lee, Jenny H.

AU - Chandler, David

AU - Wang, Yinan

AU - Pflueger, Christian

AU - Long, Georgina V.

AU - Scolyer, Richard A.

AU - Carlino, Matteo S.

AU - Menzies, Alexander M.

AU - Kefford, Richard F.

AU - Rizos, Helen

N1 - Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2019/11/25

Y1 - 2019/11/25

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.

KW - Melanoma

KW - methylation

KW - CtDNA

KW - ddPCR

KW - bisulfite conversion

UR - http://purl.org/au-research/grants/nhmrc/1093017

UR - http://purl.org/au-research/grants/nhmrc/1128951

UR - https://www.scopus.com/pages/publications/85076120395

U2 - 10.3390/app9235074

DO - 10.3390/app9235074

M3 - Article

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VL - 9

SP - 1

EP - 17

JO - Applied Sciences

JF - Applied Sciences

IS - 23

M1 - 5074

ER -

Hypermethylation of circulating free DNA in cutaneous melanoma

Abstract

Bibliographical note

Keywords

Access to Document

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Molecular determinants of risk, progression and treatment response in melanoma

Acquired resistance to PD1 inhibition in melanoma

Cite this

Hypermethylation of circulating free DNA in cutaneous melanoma

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Projects

Molecular determinants of risk, progression and treatment response in melanoma

Acquired resistance to PD1 inhibition in melanoma

Cite this