Abstract Library

#2982 Comprehensive Molecular Analysis Identifies Driver Mutations in Metastases of Sporadic Well-Differentiated Neuroendocrine Tumours of the Small Intestine

Introduction: Small intestinal neuroendocrine tumours (SI-NETs) represent a heterogenous group of tumours. The molecular mechanisms which contribute to progression of SI-NETs are poorly elucidated. They are considered to be molecularly distinct from neuroendocrine carcinomas (NECs), which share oncogenic pathways with adenocarcinomas.

Conference: 17th Annual ENETSConcerence (2020)

Presenting Author: Samsom K

Authors: Samsom K, van Veenendaal L, Roepman P, Kodach L, Steeghs N,

Keywords: whole genome sequencing, neuroendocrine tumour, small intestine, genetics,

#2234 High Rate of Copy-Number Alterations in Gastrointestinal and Pancreatic Neuroendocrine Tumors with Unidentified Driver Mutations

Introduction: The driving genetic alteration leading to neuroendocrine tumor (NET) development has been reported for primary tumors of pancreatic origin, but not for metastases. Moreover, even for primary tumor a significant “dark matter” remains to be explored.

Conference: 15th Annual ENETSConcerence (2018)

Presenting Author: Tirosh A

Authors: Tirosh A, Killian J, Zhu Y, Neychev V, Meltzer P,

Keywords: GEP-NET, Driver mutation, Copy-number, Metastases,

#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,

#1507 The CDK4/6 Inhibitor Palbociclib Induces Anti-proliferative Mechanisms in Gastroenteropancreatic Neuroendocrine Neoplasms In Vitro

Introduction: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors with heterogeneous molecular backgrounds and mostly unknown druggable driver mutations. Especially for the midgut NENs effective treatment options are limited. The retinoblastoma pathway is often inactive due to CDK4/6 overexpression in pancreatic NENs. Palbociclib is a FDA approved (ER-positive and HER2-negative breast cancer) cyclin-dependent kinases 4 and 6 inhibitor and might impair cell cycle progression and proliferation.

Conference: 13th Annual ENETSConcerence (2016)

Presenting Author: Briest F

Authors: Briest F, Grass I, Siegmund B, Grabowski P,

Keywords: GEP-NEN, targeted therapy, cyclin-dependent kinases 4/6,