Cell-Free DNA Methylation: The New Frontiers of Pancreatic Cancer Biomarkers’ Discovery
Abstract
:1. Introduction
2. Genetic and Epigenetic Implications of cfDNA in Cancer Diagnosis
2.1. Pitfalls in cfDNA Data Interpretation
2.2. Exploiting DNA Methylation Signatures for the Identification of Circulating cfDNA
3. cfDNA Methylation Biomarkers in Pancreatic Cancer or Pancreatic Pre-Neoplastic Conditions
3.1. cfDNA Hypomethylated or Non-Methylated Targets
3.2. cfDNA Hypermethylated Targets
Genes Useful to Identify Circulating Exocrine Pancreatic cfDNA | ||||||
---|---|---|---|---|---|---|
CUX2 | Ductal cell marker | Increased signal in PDAC | ||||
REG1A | Ductal and acing cell marker | Increasing signal in CP | ||||
Frequency of cfDNA methylation biomarkers (%) | ||||||
Gene | healthy | CP | PIN | PDAC I | PDAC II | PDAC III/IV |
ADAMTS1 | <3 | - | 25 | 25–88 | 78–90 | 55 |
BNC1 | 3–7 | 5 | 70 | 63–95 | 56–95 | 100 |
CCND2 | 17 | 82 | - | - | - | 24 |
CDKN1C | 60 | 90 | - | - | - | 27 |
MLH1 | 22 | 78 | - | - | - | 27 |
PGR (prox) | 14 | 76 | - | - | - | 37 |
SYK | 57 | 89 | - | - | - | 57 |
4. Discussion and Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AP | Acute pancreatitis |
ASA | American Society of Anesthesiologists |
cfDNA | Cell-free DNA |
CP | Chronic pancreatitis |
CTCs | Circulating tumor cells |
DNMTs | DNA methyl transferases |
HR | Hazard ratio |
IMPN | Intramucinous pancreatic neoplasia |
MHBs | Methylation haplotype blocks |
MI | Methylation index |
MSP | Methylation-specific PCR |
NGS | Next-generation sequencing |
PDAC | Pancreatic ductal adenocarcinoma |
PIN | Pancreatic intra-epithelial neoplasia |
RRBS | Reduced representation bisulfite sequencing |
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Method | |||||
---|---|---|---|---|---|
Features | MethDet-M3 | MSP | QMSP | Targeted Amplicon Sequencing | RRBS |
DNA methylation discrimination | Methylation-sensitive endonuclease | Bisulfite Treatment | Bisulfite Treatment | Bisulfite Treatment | Bisulfite Treatment |
Coverage | Medium/Low | Targeted | Targeted | Targeted | Medium |
Throughput | Medium | Low | Medium | Medium/High | High |
Analytical Sensitivity | Medium | Low | Medium | Low | Low |
Analytical Specificity | High | Low/Medium | Medium | Medium | Medium |
Advantages | Scalable (e.g., microarray) | Fast results Cost-effective | Quantitative | Scalable (e.g., NGS) Single CpG methylation status | Scalable (e.g., NGS) Single CpG methylation status |
Disadvantages | Risk of false positive/negative | Limited coverage | Limited coverage | May require extensive data analysis | Extensive data analysis |
Popularity | Unpopular | Very Popular | Popular | Popular | Popular |
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Brancaccio, M.; Natale, F.; Falco, G.; Angrisano, T. Cell-Free DNA Methylation: The New Frontiers of Pancreatic Cancer Biomarkers’ Discovery. Genes 2020, 11, 14. https://doi.org/10.3390/genes11010014
Brancaccio M, Natale F, Falco G, Angrisano T. Cell-Free DNA Methylation: The New Frontiers of Pancreatic Cancer Biomarkers’ Discovery. Genes. 2020; 11(1):14. https://doi.org/10.3390/genes11010014
Chicago/Turabian StyleBrancaccio, Mariarita, Francesco Natale, Geppino Falco, and Tiziana Angrisano. 2020. "Cell-Free DNA Methylation: The New Frontiers of Pancreatic Cancer Biomarkers’ Discovery" Genes 11, no. 1: 14. https://doi.org/10.3390/genes11010014
APA StyleBrancaccio, M., Natale, F., Falco, G., & Angrisano, T. (2020). Cell-Free DNA Methylation: The New Frontiers of Pancreatic Cancer Biomarkers’ Discovery. Genes, 11(1), 14. https://doi.org/10.3390/genes11010014