Abstract Library

#4546 Epigenetic exploration of mesenteric fibrosis indicates epigenetic disruption of DAXX is driving metastatic potential in small intestinal neuroendocrine tumours

Introduction: Up to 50% of patients diagnosed with small intestinal neuroendocrine tumours (SI-NETs) are affected by mesenteric fibrosis (MF) which has significant pathological effects and impacts patient mortality.

Conference:

Presenting Author: Webster A

Authors: Webster A, Martins M, Hodgetts H, Feelders R, Hofland L,

Keywords: DNA methylation, SI-NET, Mesenteric fibrosis, Epigenetics, Gene regulation, DAXX,

#4502 Molecular analysis of non-functioning PanNETs of the alpha lineage reveals new subtypes and mechanisms of progression

Introduction: Most pancreatic neuroendocrine tumours (PanNETs) are non-functioning. Previously, we demonstrated that small, MEN1-only mutated α-like PanNETs can be distinguished from larger ADM (mutated in ATRX, DAXX and MEN1) PanNETs based on epigenetic profiles. ADM PanNETs have shorter disease-free survival and a higher relapse risk. However, their therapeutic responses vary, underscoring group heterogeneity. ADM PanNETs remain insufficiently characterised, with potential subtype-specific progression drivers with implications for treatment choice and clinical outcome.

Conference:

Presenting Author: Avanthay S

Authors: Avanthay S, Di Domenico A, Kirchner P, Bräutigam K, Chouchane A,

Keywords: pancreas, epigenetics, progression, metastasis, DAXX, ATRX, Pan NET,

#4373 Focal adhesion kinase drives proliferation and invasion in gastrointestinal neuroendocrine tumours via modulation of transformative cell signalling and gene expression

Introduction: Focal Adhesion Kinase (FAK) is a non-receptor protein kinase that localises in both the cytoplasm and nucleus, influencing cell function through its enzymatic and scaffold activities. Through its scaffold function, FAK modulates gene expression epigenetically. Gastrointestinal neuroendocrine tumours (GI-NETs) exhibit a relatively low mutation rate, supporting the hypothesis that these malignancies may be driven epigenetically. Recently, PROTAC (PROteolysis TArgeting Chimeras) technology has enabled selective inhibition and degradation of FAK, providing a novel approach to explore its role in GI-NETs.

Conference:

Presenting Author: Gagliano T

Authors: Toffoli L, Ditsiou A, Moschioni E, Hamm V, Gagliano T,

Keywords: FAK, GI-NET, Cell Signalling, Epigenetics,

#4256 Epigenetic prediction of aging and metabolic traits provides insight into tumor biology in multi-focal ileal neuroendocrine tumors

Introduction: Approximately half of small intestinal neuroendocrine tumors (siNETs) are multifocal, and recent investigations into the genetic architecture of these tumors have found that they are not clonal. Due to the low mutational rate and slow growing nature of these small tumors, the ‘timing’ of the development of individual tumors has not been possible.

Conference:

Presenting Author:

Authors: Webster A, Makinen N, Ecker S, Beck S, Nakakura E,

Keywords: DNA methylation, Epigenetics, Multifocal Ileal Neuroendocrine Tumor, Multifocal Small Instestinal NET, Metabolic Traits,

#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,