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Our initial goal was to identify DNA methylation biomarkers associated with pancreatic cancer. A genomewide methylation study was performed on DNA from pancreatic ductal adenocarcinoma (PDAC) and endocrine pancreas tumors. Validation of DNA methylation patterns and concomitant alterations in expression of gene candidates was performed on patient samples and pancreatic cancer cell lines. Furthermore, validation was done on independent data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Finally, droplet digital PCR was employed to detect DNA methylation marks in cell\u2010free (cf) DNA isolated from plasma samples of PDAC patients and cancer\u2010free blood donors. Hypermethylation of the <jats:italic>SST<\/jats:italic> gene (encoding somatostatin) and concomitant downregulation of its expression were discovered in PDAC and endocrine tumor tissues while not being present in chronic pancreatitis (inflamed) tissues and normal pancreas. Fittingly, treatment with a somatostatin agonist (octreotide) reduced cell proliferation and migration of pancreatic cancer cells. Diagnostic performance of <jats:italic>SST<\/jats:italic> methylation in a receiver operating characteristic curve analysis was 100% and 89% for tissue and plasma samples, respectively. A large body of TCGA and GEO data confirmed <jats:italic>SST<\/jats:italic> hypermethylation and downregulation in PDAC and showed a similar effect in a broad spectrum of other tumor entities. <jats:italic>SST<\/jats:italic> promoter methylation represents a sensitive and promising molecular, pan\u2010cancer biomarker detectable in tumor tissue, and liquid biopsy samples.<\/jats:p>","DOI":"10.1002\/1878-0261.12684","type":"journal-article","created":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T15:33:18Z","timestamp":1585927998000},"page":"1252-1267","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["<i>SST<\/i> gene hypermethylation acts as a pan\u2010cancer marker for pancreatic ductal adenocarcinoma and multiple other tumors: toward its use for blood\u2010based 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