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#62 Genome-wide DNA methylation profiling of pancreatic neuroendocrine tumors identifies distinct methylation profiles and differentially methylated gene promoter regions associated with low, medium and high grade tumors

Introduction: Integration of genetics and epigenetics has emerged as a powerful approach to studying cellular differentiation (Mikkelsen et al, 2009) and tumorigenesis (Shen et al, 2007). The study of DNA methylation is of particular importance in cancer, as causal involvement has been demonstrated and it is the most stable of all epigenetic modifications, making it a desirable marker for both early detection and treatment of tumors. Hypermethylation of CpG sites in gene promoter regions leads to decreased gene expression; if such a gene is a tumor suppressor, this leads to carcinogenesis. To date, there have been no studies of genome-wide DNA methylation profiling of NETs. This study sets out to determine the DNA methylation profiles of low, intermediate and high grade pancreatic NET liver metastases with the intention of identifying dysregulated biological pathways in the development of these tumors. A protocol for the analysis formalin-fixed paraffin embedded tissue (FFPE) has also been developed in order to study these tumors in significant numbers following this pilot study.

Conference: 7th Annual ENETSConcerence (2010)

Presenting Author: Thirlwell C

Authors: Thirlwell C, Eymard M, Meyer T, Davidson B, Teschendorff A,

Keywords: DNA methylation, CpG dinucleotides, genome-wide, differentially methylated region (DMR) References: Duerr EM et al Defining molecular classifications and targets in gastroenteropancreatic neuroendocrine tumors through DNA microarray analysis. Endocr,