Epigenetic Landscape of Pancreatic Neuro-Endocrine Tumors Reveals Distinct Cells of Origin and Means of Tumor Progression

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Introduction: Pancreatic Neuroendocrine Tumors (PanNETs) arise from cells of the Islets of Langerhans. The majority of PanNETs are non-functional and their cell of origin cannot be defined analysing specific hormone production. Cell of origin assessment has proven importance to identify risk factors, prevent tumour development, and tailor treatment in many malignancies. Recent data on super-enhancer signatures has suggested a potential origin of PanNET from α- or β-cells. We and others have shown that distinct epigenetic profiles assessed by DNA methylation (DNAme) characterize genomic and prognostic groups of PanNET.

Aim(s): To examine whether DNAme signatures can identify the cell of origin and reveal different pathways of progression.

Materials and methods: We analysed genome-wide DNAme data (Illumina 450K) of 125 PanNETs and of α- and β-sorted cells. Α-, β-, γ-, δ-, ε-specific transcription factor expression was analysed via Nanostring, RNAseq and immunohistochemistry in different subsets of samples.

Conference: 17th Annual ENETSConcerence (2020)

Presenting Author: Di Domenico A

Authors: Di Domenico A, Pipinikas C, Maire R, Bräutigam K, Vassella E,

Keywords: cell of origin, alpha, beta, methylation, expression, epigenetic, neuroendocrine, progression, PanNET, tumor,