Abstract Library

#4592 Uncovering cell-state heterogeneity in large-cell panNEC indicates potentially targetable aberrant brain type neuronal de-differentiation

Introduction: Classification and treatment of high-grade pancreatic neuroendocrine carcinoma (panNEC), particularly those with large-cell morphology, present significant clinical challenges due to considerable inter- and intra-patient tumour heterogeneity.

Conference:

Presenting Author: Debnath O

Authors: Debnath O, Berger H, Detjen K, Kirchner P, Marinoni I,

Keywords: pancreatic neuroendocrine carcinoma, single cell, personalised medicine,

#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,

#4258 Unanticipated heterogeneity in high-grade large-cell neuroendocrine carcinoma pinpoints cell sub-state specific therapeutic targets

Introduction: High-grade pancreatic neuroendocrine carcinoma (panNEC) pose challenges in terms of classification and treatment. While molecular genetics have made strides in deciphering significant inter-tumor heterogeneity, the extent of intra-tumoral heterogeneity and lineage plasticity remains unexplored.

Conference:

Presenting Author:

Authors: Debnath O, Detjen K, Berger H, Kirchner P, Marinoni I,

Keywords: PanNEC, Single cell RNAseq,

#4158 Transcriptomic analysis of PanNET tumor progression from microtumor to metastasis in MEN1 patients

Introduction: Pancreatic Neuroendocrine Neoplasms (PanNENs) are a major component the Multiple Endocrine Neoplasia 1 Syndrome (MEN1). Although multiple pancreatic neuroendocrine microtumors (microadenomatosis) are a histomorphological hallmark of MEN1, their molecular status compared to PanNET as well as their metastasis remains unclear.

Conference:

Presenting Author:

Authors: Chouchane A, Kirchner P, Sylvain Maire R, Schiavo Lena M, Falconi M,

Keywords: Microtumor, MEN1, PanNETs, RNAseq, Transcriptomics, Progression,

#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,