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Genetic and epigenetic alterations in pancreatic neuroendocrine tumors JOURNAL OF GASTROINTESTINAL ONCOLOGY Tirosh, A., Kebebew, E. 2020; 11 (3): 567–77

Abstract

Neuroendocrine tumors (NETs) are a heterogenous group of tumors that originate from neuroendocrine cells, mainly in the pancreas and the gastrointestinal and bronchopulmonary tracts. There has been considerable progress in our understanding of the genetic and epigenetic changes associated with pancreatic NETs (PNETs). The main genetic alterations that drive PNETs include genetic alterations in MEN1, VHL and genes involved in the mTOR pathway, DAXX and/or ATRX mutations and their association with alternative telomere lengthening, and genes involved in DNA damage repair and chromatin modification. The epigenetic alterations in PNETs are also common based on genome-wide DNA methylation profiling studies, with a high rate of CpG hypermethylation in MEN1-associated PNETs compared to sporadic and VHL-associated PNETs. Moreover, the dysregulated DNA methylation status is associated with distinct gene expression profiles. This article reviews the commonly and recently discovered genetic and epigenetic changes that are associated with PNETs, inherited PNETs, and genotype-phenotype associations, and it discusses their clinical relevance.

View details for DOI 10.21037/jgo.2020.03.11

View details for Web of Science ID 000544513800014

View details for PubMedID 32655936

View details for PubMedCentralID PMC7340809