PDX1 DNA Methylation Distinguishes Two Subtypes of Pancreatic Neuroendocrine Neoplasms with a Different Prognosis

Cancers
Gitta BoonsKen Op de Beeck

Abstract

DNA methylation is a crucial epigenetic mechanism for gene expression regulation and cell differentiation. Furthermore, it was found to play a major role in multiple pathological processes, including cancer. In pancreatic neuroendocrine neoplasms (PNENs), epigenetic deregulation is also considered to be of significance, as the most frequently mutated genes have an important function in epigenetic regulation. However, the exact changes in DNA methylation between PNENs and the endocrine cells of the pancreas, their likely cell-of-origin, remain largely unknown. Recently, two subtypes of PNENs have been described which were linked to cell-of-origin and have a different prognosis. A difference in the expression of the transcription factor PDX1 was one of the key molecular differences. In this study, we performed an exploratory genome-wide DNA methylation analysis using Infinium Methylation EPIC arrays (Illumina) on 26 PNENs and pancreatic islets of five healthy donors. In addition, the methylation profile of the PDX1 region was used to perform subtyping in a global cohort of 83 PNEN, 2 healthy alpha cell and 3 healthy beta cell samples. In our exploratory analysis, we identified 26,759 differentially methylated CpGs and 79 differen...Continue Reading

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Citations

Feb 11, 2021·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Jiangman LiuJingshan Shi
Jul 10, 2021·Cancer Cytopathology·Christopher M Heaphy, Christopher J VandenBussche
Sep 25, 2021·The American Journal of Surgical Pathology·Wenzel M HackengLodewijk A A Brosens
Nov 12, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gitta BoonsKen Op de Beeck

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Methods Mentioned

BETA
acetylation
methylation profiling
Chip
immunoprecipitation
Assay

Software Mentioned

dendextend
Chip Analysis Methylation Pipeline ( ChAMP )
Minfi
R
methylGSA package
GREAT
conumee package
Genomic Regions Enrichment of Annotations Tool ( GREAT )
conumee
limma

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