Abstract Library

#2126 Histone Replacement in Cancer: Dissecting the Role of H3.3 Chaperones in Pancreatic Tumorigenesis

Introduction: Cancer driver mutations affecting the histone H3.3 chromatin remodellers ATRX and DAXX were recently discovered in 43% of sporadic pancreatic neuroendocrine tumours (PNET). Progressive age-dependent replacement of canonical H3.1/2 with H3.3 is crucial for maintaining genome integrity through expression of repressive markers at heterochromatic sites, where loading is mediated by ATRX and DAXX. Loss of H3.3 chaperones in PNET is associated with activation of ALT, a telomere maintenance mechanism, eventually leading to chromosome instability. It has been suggested that ATRX/DAXX expression is necessary for repressing ALT, but mechanistic details of this interaction are not fully understood.

Conference: 15th Annual ENETSConcerence (2018)

Presenting Author: Sposito T

Authors: Sposito T, C Nguyen Tu M, Thirlwell C, Salomoni P,

Keywords: PNET, mouse model, epigenetic,

#1256 Characterization and Rescue of a Pathogenic D63N Mutant Human Glucagon Receptor That Causes a Pancreatic Neuroendocrine Tumor Syndrome (Mahvash disease)

Introduction: We have previously demonstrated that inactivating glucagon receptor (GCGR) mutations cause a novel hereditary human disease of hyperglucagonemia, pancreatic α cell hyperplasia, and pancreatic neuroendocrine tumor (Mahvash disease). We recently identified a novel missense GCGR mutation, D63N, in a family with Mahvash disease.

Conference: 13th Annual ENETSConcerence (2016)

Presenting Author: Yu R

Authors: Yu R, Zhou C, Chen C,

Keywords: Mutant glucagon receptor, chaperone, Mahvash disease,

#629 Targeting Chaperone Activity and Chaperone Expression in Human GEP-NET Cells Can Repress Their Proliferation and Sensitize Them to Chemotherapy

Introduction: New approaches for better treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are acutely needed. Inhibitors of chaperone activity of heat shock protein 90 (Hsp90) seem to be promising agents but they upregulate cytoprotective chaperones Hsp70 and Hsp27.

Conference: 10th Annual ENETSConcerence (2013)

Presenting Author:

Authors: Demidkina A, Kudryavtsev V, Mosina V, Kabakov A,

Keywords: chemosensitization, heat shock protein, 17AAG,