DNA Hypermethylation as a Blood-Based Marker for Pancreatic Cancer

Henriksen, Stine Dam; Madsen, Poul Thøis; Krarup, Henrik; Thorlacius-Ussing, Ole

doi:10.1097/mpa.0000000000000487

Cited by 31 publications

(27 citation statements)

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“…The genes were primarily selected based on a literature review performed by our group prior to this study [16]. The genes selected for the panel had previously been detected as hypermethylated in either cell-free DNA in plasma or serum, pancreatic juice or tumour tissue from patients with pancreatic cancer and in addition unmethylated in samples from healthy individuals.…”

Section: Methodsmentioning

confidence: 99%

“…DNA hypermethylation can be detected in cell-free DNA in plasma and serum and is potentially tumour specific and useable as blood-based diagnostic markers for pancreatic cancer [14–16]. …”

Section: Introductionmentioning

confidence: 99%

“…Thus far, only a few studies with small numbers of patients have evaluated cell-free DNA hypermethylation as a blood-based marker for pancreatic cancer, testing the methylation status of only a single gene or small gene panel [16]. These data have shown a significant difference in DNA hypermethylation between patients with pancreatic cancer and healthy controls [4, 17].…”

Section: Introductionmentioning

confidence: 99%

“…However, the studies had difficulties in differentiating between malignant and benign pancreatic disease [4]. None of the previously examined genes have the potential to serve as an individual diagnostic marker [16]. When developing and testing a biomarker for pancreatic cancer, inclusion of relevant control groups with benign pancreatic disease is very important to enable differentiation of pancreatic cancer-specific hypermethylation and hypermethylation related to pancreatic disease in general [16].…”

Section: Introductionmentioning

confidence: 99%

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Cell-free DNA promoter hypermethylation in plasma as a diagnostic marker for pancreatic adenocarcinoma

et al. 2016

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BackgroundPancreatic cancer has a 5-year survival rate of only 5–7%. Difficulties in detecting pancreatic cancer at early stages results in the high mortality and substantiates the need for additional diagnostic tools. Surgery is the only curative treatment and unfortunately only possible in localized tumours. A diagnostic biomarker for pancreatic cancer will have a major impact on patient survival by facilitating early detection and the possibility for curative treatment. DNA promoter hypermethylation is a mechanism of early carcinogenesis, which can cause inactivation of tumour suppressor genes. The aim of this study was to examine promoter hypermethylation in a panel of selected genes from cell-free DNA, as a diagnostic marker for pancreatic adenocarcinoma.MethodsPatients with suspected or biopsy-verified pancreatic cancer were included prospectively and consecutively. Patients with chronic/acute pancreatitis were included as additional benign control groups. Based on an optimized accelerated bisulfite treatment protocol, methylation-specific PCR of a 28 gene panel was performed on plasma samples. A diagnostic prediction model was developed by multivariable logistic regression analysis using backward stepwise elimination.ResultsPatients with pancreatic adenocarcinoma (n = 95), chronic pancreatitis (n = 97) and acute pancreatitis (n = 59) and patients screened, but negative for pancreatic adenocarcinoma (n = 27), were included. The difference in mean number of methylated genes in the cancer group (8.41 (95% CI 7.62–9.20)) vs the total control group (4.74 (95% CI 4.40–5.08)) was highly significant (p < 0.001). A diagnostic prediction model (age >65, BMP3, RASSF1A, BNC1, MESTv2, TFPI2, APC, SFRP1 and SFRP2) had an area under the curve of 0.86 (sensitivity 76%, specificity 83%). The model performance was independent of cancer stage.ConclusionsCell-free DNA promoter hypermethylation has the potential to be a diagnostic marker for pancreatic adenocarcinoma and differentiate between malignant and benign pancreatic disease. This study brings us closer to a clinical useful diagnostic marker for pancreatic cancer, which is urgently needed. External validation is, however, required before the test can be applied in the clinic.Trial registrationClinicalTrials.gov, NCT02079363 Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0286-2) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cell-free DNA promoter hypermethylation in plasma as a diagnostic marker for pancreatic adenocarcinoma

et al. 2016

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“…In more than 80% of the IPMNs, it is reported that tumor suppressor gene expression by promoter hypermethylation at CpG islands is silenced. Interestingly, higher grade IPMNs possess a highest number of methylated genes than lower grade IPMNs (63). Significantly, the mismatch repair genes MutL homolog 1 (hMLH1) and O 6 -alkylguanine DNA alkyltransferase (MGMT) are found more frequently methylated in the higher grade IPMNs than in lower grade IPMNs (64).…”

Section: Current Practice and The Updates On The Genomic Fieldmentioning

confidence: 99%

Updates and Critical Evaluation on Novel Biomarkers for the Malignant Progression of Intraductal Papillary Mucinous Neoplasms of the Pancreas

Moris

Damaskos

Spartalis

et al. 2017

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A comprehensive review of the genetic and biological evidence supports a role for MicroRNA‐137 in the etiology of schizophrenia

Sakamoto

Crowley

2017

American J of Med Genetics Pt B

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Since it was first associated with schizophrenia (SCZ) in a 2011 genome-wide association study (GWAS), there have been over 100 publications focused on MIR137, the gene encoding microRNA-137. These studies have examined everything from its fundamental role in the development of mice, flies, and fish to the intriguing enrichment of its target gene network in SCZ. Indeed, much of the excitement surrounding MIR137 is due to the distinct possibility that it could regulate a gene network involved in SCZ etiology, a disease which we now recognize is highly polygenic. Here we comprehensively review, to the best of our ability, all published genetic and biological evidence that could support or refute a role for MIR137 in the etiology of SCZ. Through a careful consideration of the literature, we conclude that the data gathered to date continues to strongly support the involvement of MIR137 and its target gene network in neuropsychiatric traits, including SCZ risk. There remain, however, more unanswered than answered questions regarding the mechanisms linking MIR137 genetic variation with behavior. These questions need answers before we can determine whether there are opportunities for diagnostic or therapeutic interventions based on MIR137. We conclude with a number of suggestions for future research on MIR137 that could help to provide answers and hope for a greater understanding of this devastating disorder.

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DNA Hypermethylation as a Blood-Based Marker for Pancreatic Cancer

Cited by 31 publications

References 0 publications

Cell-free DNA promoter hypermethylation in plasma as a diagnostic marker for pancreatic adenocarcinoma

Cell-free DNA promoter hypermethylation in plasma as a diagnostic marker for pancreatic adenocarcinoma

Updates and Critical Evaluation on Novel Biomarkers for the Malignant Progression of Intraductal Papillary Mucinous Neoplasms of the Pancreas

A comprehensive review of the genetic and biological evidence supports a role for MicroRNA‐137 in the etiology of schizophrenia

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