Novel von Hippel-Lindau-related pancreatic neuroendocrine neoplasms in-vivo model

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Introduction: Von Hippel-Lindau (VHL) disease is a familial cancer syndrome caused by a germline mutation in the VHL tumor suppressor gene. Although VHL-related pancreatic neuroendocrine neoplasms (vPNEN) have been reported, their molecular pathogenesis is not fully investigated.

Aim(s): To generate a mice model for studying the mechanisms that promote vPNEN development in-vivo.

Materials and methods: We induced a frameshift mutation in VHL using CRISPR/Cas9 technique in BON1 cell line, originating from PNEN (FS-BON1). We validated the pseudohypoxic nature of the cells by real time polymerase chain reaction of VEGF and EPO in FS-BON1 and VHL wild type BON1 (WT-BON1). We compared growth of cell line derived xenografts (CDXs) in athymic Nude-Foxn1nu female mice, in three groups: WT-BON1 (n=9), FS-BON1 (n=9) and media (purified bovine serum, n=5). Tumor diameter and calculated volume and mice weight were measured weekly. Plasma chromogranin A (CgA) levels were measured in mice serums by ELISA.

Conference:

Presenting Author:

Authors: Telerman A, Yossef Y, Chmelnik A, Tirosh A,

Keywords: VHL, PNEN, BON1, pseudohypoxia, CDX,