Next Article in Journal
Dysregulated MicroRNA Expression Profiles and Potential Cellular, Circulating and Polymorphic Biomarkers in Non-Hodgkin Lymphoma
Next Article in Special Issue
Familial Lung Cancer: A Brief History from the Earliest Work to the Most Recent Studies
Previous Article in Journal
microRNA Expression in Sentinel Nodes from Progressing Melanoma Patients Identifies Networks Associated with Dysfunctional Immune Response
Previous Article in Special Issue
Methylation Analysis of DNA Mismatch Repair Genes Using DNA Derived from the Peripheral Blood of Patients with Endometrial Cancer: Epimutation in Endometrial Carcinogenesis
Article Menu

Export Article

Open AccessArticle
Genes 2016, 7(12), 125; doi:10.3390/genes7120125

Evaluation of Methylation Biomarkers for Detection of Circulating Tumor DNA and Application to Colorectal Cancer

1
CSIRO Food and Nutrition, P.O. Box 52, North Ryde, NSW 1670, Australia
2
Clinical Genomics Pty Ltd., North Ryde, NSW 2113, Australia
3
Flinders Centre for Innovation in Cancer, Flinders University of South Australia, GPO Box 2100, Adelaide, SA 5001, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Selvarangan Ponnazhagan
Received: 10 August 2016 / Revised: 3 November 2016 / Accepted: 29 November 2016 / Published: 15 December 2016
(This article belongs to the Special Issue Cancer Genetics)
View Full-Text   |   Download PDF [1567 KB, uploaded 15 December 2016]   |  

Abstract

Solid tumors shed DNA into circulation, and there is growing evidence that the detection of circulating tumor DNA (ctDNA) has broad clinical utility, including monitoring of disease, prognosis, response to chemotherapy and tracking tumor heterogeneity. The appearance of ctDNA in the circulating cell-free DNA (ccfDNA) isolated from plasma or serum is commonly detected by identifying tumor-specific features such as insertions, deletions, mutations and/or aberrant methylation. Methylation is a normal cell regulatory event, and since the majority of ccfDNA is derived from white blood cells (WBC), it is important that tumour-specific DNA methylation markers show rare to no methylation events in WBC DNA. We have used a novel approach for assessment of low levels of DNA methylation in WBC DNA. DNA methylation in 29 previously identified regions (residing in 17 genes) was analyzed in WBC DNA and eight differentially-methylated regions (DMRs) were taken through to testing in clinical samples using methylation specific PCR assays. DMRs residing in four genes, BCAT1, GRASP, IKZF1 and IRF4, exhibited low positivity, 3.5% to 7%, in the plasma of colonoscopy-confirmed healthy subjects, with the sensitivity for detection of ctDNA in colonoscopy-confirmed patients with colorectal cancer being 65%, 54.5%, 67.6% and 59% respectively. View Full-Text
Keywords: hypermethylation; biomarkers; colorectal cancer; plasma; BCAT1; GRASP; IKZF1; IRF4 SDC2; SEPT9; epigenetics; circulating tumor DNA; liquid biopsy hypermethylation; biomarkers; colorectal cancer; plasma; BCAT1; GRASP; IKZF1; IRF4 SDC2; SEPT9; epigenetics; circulating tumor DNA; liquid biopsy
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary materials

  • Supplementary File 1:

    ZIP-Document (ZIP, 284 KB)

  • Externally hosted supplementary file 1
    Link: http://none
    Description: Supplementary Tables and Figure

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Mitchell, S.M.; Ho, T.; Brown, G.S.; Baker, R.T.; Thomas, M.L.; McEvoy, A.; Xu, Z.-Z.; Ross, J.P.; Lockett, T.J.; Young, G.P.; LaPointe, L.C.; Pedersen, S.K.; Molloy, P.L. Evaluation of Methylation Biomarkers for Detection of Circulating Tumor DNA and Application to Colorectal Cancer. Genes 2016, 7, 125.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Genes EISSN 2073-4425 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top