Abstract Library

#4604 Germline predisposition to neuroendocrine tumours of the pancreas (pNEN) based on mutations in DNA repair genes – BRCA1, BRCA2, PALB2, CHEK2, MLH1, MSH2, MSH6, PMS2, EPCAM, APC, MUTYH, STK11

Introduction: Neuroendocrine tumours of the pancreas (pNEN) rank as the second most common epithelial neoplasms after pancreatic adenocarcinoma, with increasing prevalence and a mortality rate of 60%. Identifying germline mutations in DNA repair genes such as CHEK2, BRCA1/2, and MUTYH within pNEN cases may pave the way for personalised diagnostics and therapies.

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Presenting Author:

Authors: Jurecka Lubieniecka B, Ros-Mazurczyuk M, Oczko-Wojciechowska M, Cortez A, Handkiewicz-Junak D,

Keywords: pNEN, DNA repair genes,

#4468 Prevalence of familial pheochromocytoma and paraganglioma syndromes – A large multicentre study

Introduction: Pheochromocytoma and paraganglioma (PPGLs) are rare tumours. Depending on the studied population, approximately 30% of PPGLs are caused by a germline pathogenic variant (PV).

Conference:

Presenting Author: Halperin R

Authors: Halperin R, Reznick-Levi G, Khalaileh A, Svirsky-Frayden R, Reish O,

Keywords: paraganglioma, pheochromocytoma, genetic evaluation, catecholamine, sdhb, vhl,

#4378 Hypoxic signalling in pancreatic NETs (pNETs)

Introduction: In a genomic profiling study conducted as part of the COMPOSE Phase III multicentre open-labelled clinical trial we assessed 9 pNET patients, 2 of which showed upregulation of CA9 and hypoxic signalling. Hypoxic tumour cells present CA9 for extracellular proton channelling, maintenance of intracellular pH and to acidify and thereby vascularise and immune-suppress the TME. In normoxia, EGLN1-3 hydroxylate proline residues of HIF1A for its subsequent ubiquitination by the VHL-complex resulting in degradation and repression of its target genes.

Conference:

Presenting Author: Walter T

Authors: Walter T, Smutna V, Srirajaskanthan R, Capdevila J, Qin Y,

Keywords: hypoxia, pNET, HIF1A, CA9, Case study, hypoxic, genomic profiling,

#3848 LITESPARK-015 cohort B1 – A phase 2 open-label study of Belzutifan (a HIF-2α inhibitor) monotherapy in patients with von Hippel-Lindau (VHL) disease–associated tumors

Introduction: Patients (pts) with von Hippel-Lindau (VHL) disease need novel targeted therapies. Hypoxia-inducible factor 2α (HIF-2α) is a key oncogenic driver in VHL disease. Belzutifan (MK-6482), a HIF-2α inhibitor, has shown antitumor activity in pts with advanced renal cell carcinoma (RCC) and pancreatic neuroendocrine tumors (pNETs); more data are needed in VHL disease–associated localized tumors.

Conference:

Presenting Author:

Authors: Walter T, Gong K, Nakamura E, Iliopoulos O, Jimenez C,

Keywords: von Hippel-Lindau disease, belzutifan, MK-6482,

#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.

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Presenting Author:

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

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