1. SUN-115 Distinct DNA Methylation Signature in Neuroendocrine Tumors of Different Primary Sites and Hereditary Predisposition
- Author
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Lee S. Weinstein, Paul S. Meltzer, Amit Tirosh, Sunita K. Agarwal, Electron Kebebew, Yuelin Jack Zhu, Jonathan Keith Killian, Naris Nilubol, Petersen David, Jenny E Blau, and Dhaval Patel
- Subjects
endocrine system diseases ,Primary sites ,Tumor Biology: Diagnostics, Therapies, Endocrine Neoplasias, and Hormone Dependent Tumors ,Endocrinology, Diabetes and Metabolism ,DNA methylation ,medicine ,Cancer research ,Tumor Biology ,Neuroendocrine tumors ,Biology ,medicine.disease ,Signature (topology) ,AcademicSubjects/MED00250 - Abstract
Objective There is scant data of the genome-wide methylome alterations in neuroendocrine tumors (NET). Thus, the goal of this study was to compare the DNA methylation signature of NETs with respect to various primary sites and inherited genetic predisposition syndromes including von Hippel-Lindau (VHL) and multiple endocrine neoplasia type 1 (MEN1). Methods Genome-wide DNA methylation analysis of 96 NETs (primary and metastatic) was performed by using the Illumina Infinium EPIC Array. Principal component analysis (PCA) and unsupervised clustering analyses were performed to identify distinct methylome signatures. The methylation status of genetic drivers such as APC were assessed by primary site. Results A total of 835,424 CpGs methylation sites were quantified. Hypermethylated CpG sites were detected more frequently in sporadic vs. MEN1-related vs. VHL-related NETs, respectively (p < 0.001 for all comparisons), while hypomethylated CpGs sites were more common in VHL-related NETs vs. sporadic and MEN1-related NETs (p Small-intestinal NETs (SINETs) had the most differences at CpGs with the highest number of hyper- and hypomethylated CpG sites, followed by duodenal NETs (DNETs) and pancreatic NETs (PNETs, p Conclusion Various primary NET sites and genetically predisposed MEN1-related NETs have distinct DNA CpG methylation signatures. The methylome signatures identified in this study may be useful for non-invasive molecular characterization of NETs, through DNA methylation profiling of biopsy samples or circulating tumor DNA. more...
- Published
- 2020