biostudies-literatureFujikura KAmerican Cancer SocietyNIDDK NIH HHSNational Institute of Diabetes and Digestive and Kidney DiseasesNational Cancer InstituteNCI NIH HHSAmerican Gastroenterological AssociationAmerican Association for Cancer ResearchSidney Kimmel Foundation for Cancer Research279-288https://www.ebi.ac.uk/biostudies/studies/S-EPMC9516434biostudies-literatureUnknown254(3)Epigenetic alterations are increasingly recognized as important contributors to the development and progression of pancreatic ductal adenocarcinoma. 5-hydroxymethylcytosine (5hmC) is an epigenetic DNA mark generated through the ten-eleven translocation (TET) enzyme-mediated pathway and is closely linked to gene activation. However, the timing of alterations in epigenetic regulation in the progression of pancreatic neoplasia is not well understood. In this study, we hypothesized that aberrant expression of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) and subsequent global 5hmC alteration are linked to early tumorigenesis in the pancreas. Therefore, we evaluated alterations of 5hmC and TET1 levels using immunohistochemistry in pancreatic neoplasms (n = 380) and normal ducts (The Journal of pathologyDownregulation of 5-hydroxymethylcytosine is an early event in pancreatic tumorigenesis.PMC9516434P30 CA006973AGA‐Bernard Lee Schwartz Foundation Research ScholK08 DK107781American Cancer Society ‐ The Cornelia T. Bailey FP50 CA062924AACR‐Incyte Corporation Career Development Award fP50 CA62924Goggins MGAlruwaii ZIMeeker AKHe JDing DWright MMacgregor-Das AHruban RHFujikura KRoberts NJHong SMHaffner MCRoy SWood LDTrujillo MAfalseDownregulation of 5-hydroxymethylcytosine is an early event in pancreatic tumorigenesis.Epigenetic alterations are increasingly recognized as important contributors to the development and progression of pancreatic ductal adenocarcinoma. 5-hydroxymethylcytosine (5hmC) is an epigenetic DNA mark generated through the ten-eleven translocation (TET) enzyme-mediated pathway and is closely linked to gene activation. However, the timing of alterations in epigenetic regulation in the progression of pancreatic neoplasia is not well understood. In this study, we hypothesized that aberrant expression of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) and subsequent global 5hmC alteration are linked to early tumorigenesis in the pancreas. Therefore, we evaluated alterations of 5hmC and TET1 levels using immunohistochemistry in pancreatic neoplasms (n = 380) and normal ducts (2021-01-01T00:00:00Z2021 Jul2025-04-19T05:15:49.169Z2025-04-19T05:15:49.169ZS-EPMC95164343387050910.1002/path.5682