Hypermethylation of Circulating Free DNA in Cutaneous Melanoma
Source abstract
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.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Cancer Genomics and Diagnostics · Epigenetics and DNA Methylation · Renal cell carcinoma treatment
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia
Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2065, Australia
Australian Genome Research Facility, Victorian Comprehensive Cancer Centre, 305 Grattan St, Melbourne, VIC 3000, Australia
Australian Research Council Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, Australia
Harry Perkins Institute of Medical Research, Nedlands, WA 6009, Australia
Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia
Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia
Department of Medical Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, NSW 2065, Australia
Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, NSW 2050, Australia
Crown Princess Mary Cancer Centre, Westmead and Blacktown hospitals, Sydney, NSW 2145, Australia
Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia
Funding
National Health and Medical Research Council
References (51)
Show source-provided references
1. Mathai, R.A., Vidya, R.V.S., Reddy, B.S., Thomas, L., Udupa, K., Kolesar, J., and Rao, M. (2019). Potential utility of liquid biopsy as a diagnostic and prognostic tool for the assessment of solid tumors: Implications in the precision oncology. J. Clin. Med., 8.10.3390/jcm8030373 ↗
2. Liquid biomarkers in melanoma: Detection and discovery10.1186/s12943-018-0757-5 ↗
3. Barbany, G., Arthur, C., Lieden, A., Nordenskjold, M., Rosenquist, R., Tesi, B., Wallander, K., and Tham, E. (2019). Cell free tumour DNA testing for early detection of cancer-a potential future tool. J. Intern. Med.10.1111/joim.12897 ↗
4. Detection of circulating tumor DNA in early- and late-stage human malignancies10.1126/scitranslmed.3007094 ↗
5. Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: A proof-of-concept study10.1093/annonc/mdx212 ↗
6. Circulating tumour DNA predicts response to anti-PD1 antibodies in metastatic melanoma10.1093/annonc/mdx026 ↗
7. Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma10.18632/oncotarget.5788 ↗
8. Analysis of circulating tumor DNA to monitor metastatic breast cancer10.1056/NEJMoa1213261 ↗
9. Discovery of targetable genetic alterations in advanced non-small cell lung cancer using a next-generation sequencing-based circulating tumor DNA assay10.1038/s41598-017-14962-0 ↗
10. Circulating tumor DNA profiling by next generation sequencing reveals heterogeneity of crizotinib resistance mechanisms in a gastric cancer patient with MET amplification10.18632/oncotarget.15457 ↗
11. Detection of therapeutically targetable driver and resistance mutations in lung cancer patients by next-generation sequencing of cell-free circulating tumor DNA10.1158/1078-0432.CCR-16-1231 ↗
12. Prediction and monitoring of relapse in stage III melanoma using circulating tumor DNA10.1093/annonc/mdz048 ↗
13. Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients10.1093/annonc/mdz075 ↗
14. Monitoring melanoma using circulating free DNA10.1007/s40257-018-0398-x ↗
15. The emerging role of cell-free DNA as a molecular marker for cancer management10.1016/j.bdq.2019.100087 ↗
16. Detection of solid tumor molecular residual disease (MRD) using circulating tumor DNA (ctDNA)10.1007/s40291-019-00390-5 ↗
17. Tumor-specific methylations in circulating cell-free DNA as clinically applicable markers with potential to substitute mutational analyses10.1080/14737159.2018.1545576 ↗
18. Gai, W., and Sun, K. (2019). Epigenetic Biomarkers in Cell-Free DNA and Applications in Liquid Biopsy. Genes, 10.10.3390/genes10010032 ↗
19. Liquid biopsies: DNA methylation analyses in circulating cell-free DNA10.1016/j.jgg.2018.02.007 ↗
20. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma10.1038/nmat4997 ↗
21. Genome-scale detection of hypermethylated CpG islands in circulating cell-free DNA of hepatocellular carcinoma patients10.1038/cr.2015.126 ↗
22. Cancer epigenetics reaches mainstream oncology10.1038/nm.2305 ↗
23. Comparative analysis of 12 different kits for bisulfite conversion of circulating cell-free DNA10.1080/15592294.2017.1334024 ↗
24. Wouters, J., Vizoso, M., Martinez-Cardus, A., Carmona, F.J., Govaere, O., Laguna, T., Joseph, J., Dynoodt, P., Aura, C., and Foth, M. (2017). Comprehensive DNA methylation study identifies novel progression-related and prognostic markers for cutaneous melanoma. BMC Med., 15.10.1186/s12916-017-0851-3 ↗
25. CpG island methylator phenotype predicts progression of malignant melanoma10.1158/1078-0432.CCR-08-1361 ↗
26. Targeted methylation sequencing of plasma cell-free DNA for cancer detection and classification10.1093/annonc/mdy119 ↗
27. Methylation patterns in serum DNA for early identification of disseminated breast cancer10.1186/s13073-017-0499-9 ↗
28. The potential of circulating tumor DNA methylation analysis for the early detection and management of ovarian cancer10.1186/s13073-017-0500-7 ↗
29. Circulating tumour DNA (ctDNA) as a liquid biopsy for melanoma10.1016/j.canlet.2017.06.030 ↗
30. Epigenetics of malignant melanoma10.1016/j.semcancer.2017.10.006 ↗
31. Andrews, S. (2018, May 28). FastQC: A Quality Control Tool for High Throughput Sequence Data. Available online: http://www.bioinformatics.babraham.ac.uk/projects/fastqc/.
32. Fastp: An ultra-fast all-in-one FASTQ preprocessor10.1093/bioinformatics/bty560 ↗
33. Bismark: A flexible aligner and methylation caller for Bisulfite-Seq applications10.1093/bioinformatics/btr167 ↗
34. Fast gapped-read alignment with Bowtie 210.1038/nmeth.1923 ↗
35. Karolchik, D., Hinrichs, A.S., and Kent, W.J. (2011). The UCSC genome browser. Curr. Protoc. Hum. Genet.10.1002/0471142905.hg1806s71 ↗
36. Shao, C., Dai, W., Li, H., Tang, W., Jia, S., Wu, X., and Luo, Y. (2017). The relationship between RASSF1A gene promoter methylation and the susceptibility and prognosis of melanoma: A meta-analysis and bioinformatics. PLoS ONE, 12.10.1371/journal.pone.0171676 ↗
37. Promoter methylation as biomarkers for diagnosis of melanoma: A systematic review and meta-analysis10.1002/jcp.27495 ↗
38. Aberrant DNA methylation is associated with aggressive clinicopathological features and poor survival in cutaneous melanoma
39. Genome-wide promoter methylation analysis identifies epigenetic silencing of MAPK13 in primary cutaneous melanoma10.1111/pcmr.12096 ↗
40. Tumor-related methylated cell-free DNA and circulating tumor cells in melanoma
41. CpG island methylation profiling in human melanoma cell lines10.1097/CMR.0b013e32832b274e ↗
42. Aberrant DNA methylation in melanoma: Biomarker and therapeutic opportunities10.1186/s13148-017-0332-8 ↗
43. Comparison of whole-genome bisulfite sequencing library preparation strategies identifies sources of biases affecting DNA methylation data10.1186/s13059-018-1408-2 ↗
44. Degradation of DNA by bisulfite treatment10.1016/j.bmcl.2007.01.040 ↗
45. Characterizing the strand-specific distribution of non-CpG methylation in human pluripotent cells10.1093/nar/gkt1306 ↗
46. Hairpin-bisulfite PCR: Assessing epigenetic methylation patterns on complementary strands of individual DNA molecules10.1073/pnas.2536758100 ↗
47. Dynamic changes in the human methylome during differentiation10.1101/gr.101907.109 ↗
48. Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma10.1200/JCO.2013.49.8691 ↗
49. Paraoxonase 3 is involved in the multi-drug resistance of esophageal cancer10.1186/s12935-018-0657-1 ↗
50. Prostate tumor DNA methylation is associated with cigarette smoking and adverse prostate cancer outcomes10.1002/cncr.30045 ↗
51. Identification of predictive DNA methylation biomarkers for chemotherapy response in colorectal cancer10.3389/fphar.2017.00047 ↗