Epigenetic progression steps in alpha-lineage MEN1-DAXX/ATRX mutated Pancreatic Neuroendocrine Tumors (PanNET)

#3388

Introduction: Recently, based on DNA methylation profiles, we have hypothesized that PanNETs with mutations in ATRX, DAXX and MEN1 originate from α-cells. Alpha-like PanNETs, small and indolent, were enriched for mutations in MEN1 only, while epigenetically intermediate PanNETs, larger and with high relapse risk, showed mutations in both MEN1 and DAXX/ATRX (Int-ADM). Int-ADM PanNETs show progressive loss of alpha cell differentiation.

Aim(s): To dissect epigenetic changes and activation of related pathways, occurring during a potential progression from a-like PanNET to more aggressive Int-ADM.

Materials and methods: We analysed DNA methylation profiles of 155 PanNET including samples from our institution and from publicly available studies. RNA sequencing data were obtained for 42 of these tumors.

Conference:

Presenting Author: Marinoni I

Authors: Di Domenico A, Kirchner P, Maire R, Thirlwell C, Perren A,

Keywords: Epigenetics, DAXX/ATRX, PanNET, PanNET progression,