Abstract Library

#4583 Improved assessment of gene rearrangements by targeting non-coding DNA regions in patients diagnosed with pancreatic neuroendocrine neoplasms

Introduction: Whole-genome sequencing projects documented the heterogeneity of pancreatic neuroendocrine neoplasms (PanNEN), while showing that few core pathways are consistently affected in their tumorigenesis. Comprehensive genomic profiling (CGP) of real-world cases is expected to recapitulate such heterogeneity for patient stratification and to inform precision therapy. While coding DNA is the focus of current CGP panels, the potential of targeting non-coding DNA (ncDNA) to improve structural variants detection has not been widely explored in this context.

Conference:

Presenting Author: Agnoletto C

Authors: Agnoletto C, Trevisani E, Borghesani M, Landoni L, Luchini C,

Keywords: neuroendocrine, non-coding DNAs, structural variants, clinical relevance, CGP panel,

#4227 Evaluation of circulating extracellular vesicles as suitable prognostic markers in MEN1-associated non-functioning pancreatic neuroendocrine neoplasia

Introduction: Non-functioning pancreatic neuroendocrine neoplasias (NF-pNENs) significantly contribute to premature death of multiple endocrine neoplasia type 1 (MEN1) patients. Reliable prognostic markers for disease progression are lacking. Circulating liquid biomarkers, including microRNAs and Long-non-Coding (LnC) RNAs in extracellular vesicles, are emerging as new prognostic tools.

Conference:

Presenting Author:

Authors: Manoharan J, Khizanishvili N, Krasser-Gercke N, Albers M, Mintziras I,

Keywords: Multiple endokrine neoplasia type 1, Extracellular vesicles, Non-functioning pancreatic neuroendocrine neoplasia, exosomal-LnC-RNA NEAT1, exosomal miRNA451a,

#4157 Decoding and targeting of metabolic heterogeneity in pancreatic neuroendocrine tumors (PanNETs): MCT1 and MCT4 in the crosshair for precision therapy

Introduction: Mechanisms driving progression from indolent to aggressive and metastatic disease in PanNET are largely unknown. Recent transcriptome and epigenome analyses suggest a stepwise progression model leading to enhanced proliferation, de-differentiation, and metabolic reprogramming. However, the metabolic landscape at different stages and the therapeutic potential of targeting metabolic proteins remain largely uncharacterized.

Conference:

Presenting Author: Sadowski M

Authors: Bräutigam K, Straub J, Bihi A, Andreasi V, Kirchner P,

Keywords: metabolic heterogeneity, 3D model, precision medicine, metabolic subtype, PanNET, hypoxia, lactate efflux, microvessel density, MCT1/MCT4,

#4124 Evaluating a possible association between promoter methylation level of genes encoding catecholamine metabolizing enzymes and metanephrine secretion in pheochromocytoma and paraganglioma

Introduction: Paragangliomas (PPGLs) are rare neuroendocrine tumors that may secrete catecholamines and their metabolites (metanephrines [MN], normetanephrine [NMN]). Secretion patterns differ by adrenal/extra-adrenal origin and genetic alteration. Catecholamines synthesis is carried by phenylalanine hydroxylase (PAH), tyrosine hydroxylase (TH), aromaticL-aminoacid decarboxylase (AADC), dopamine β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT). However, their regulation in PPGL is not entirely understood.

Conference:

Presenting Author: Tirosh A

Authors: Kaplinsky A, Halperin R, Shlomai G, Tirosh A,

Keywords: ppgl, methylation, catecholamine, pseudohypokia, metanephrine, kinase signaling, pheochromocytoma, paraganglioima,

#3796 The effect of pseudohypoxia on the immune microenvironment of pancreatic neuroendocrine neoplasms (PanNEN)

Introduction: Pancreatic neuroendocrine tumors may develop sporadically or as part of an inherited disease, such as von Hippel-Lindau (VHL). VHL disease is caused by a germline pathogenic variant in the VHL gene encoding VHL protein (pVHL). Hypoxia inducible factor (HIF) is responsible for cellular oxygen supply. Its degradation is mediated in normoxic states via ubiquitination and inhibited by pVHL. Hence, pVHL deficiency leads to pseudohypoxia due to HIF overexpression. Several studies suggested immunomodulatory role for HIF in kidney cancer.

Conference:

Presenting Author:

Authors: Solomon Chmelnik A, Telerman A, Tirosh A,

Keywords: Pancreatic neuroendocrine tumor, VHL, DNA methylation, Immune cells, PD-L1,