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bioRxiv · 10.1101/2020.04.08.029785

Epigenetic landscape of pancreatic neuroendocrine tumours reveals distinct cells of origin and means of tumour progression

Di Domenico, A.·Pipinikas, C. P.·Maire, R. S.·Bräutigam, K.·Simillion, C.·Dettmer, M. S.·Vassella, E.·Thirlwell, C.·Perren, A.·Marinoni, I.
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Abstract

Recent data suggest that Pancreatic Neuroendocrine Tumours (PanNETs) originate from - or {beta}-cells of the islets of Langerhans. The majority of PanNETs are non-functional and do not express cell-type specific hormones. We examined whether tumour DNA methylation (DNAme) profiling combined with genomic data could identify cell of origin and reveal pathways involved in PanNET progression. We analysed genome-wide DNAme data of 125 PanNETs and sorted - and {beta}-cells. To confirm cell identity, we investigated ARX and PDX1 expression. Based on epigenetic similarities, PanNETs clustered in -like, {beta}-like and intermediate tumours. The epigenetic similarity to -cells progressively decreased in the intermediate tumours, which presented unclear differentiation. Specific transcription factor methylation and expression varied in the respective /{beta}-tumour groups. Depending on DNAme similarity to /{beta}-cells, PanNETs have different mutational spectra, stage of the disease and prognosis, indicating potential means of PanNET progression.

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Di Domenico, A., Pipinikas, C. P., Maire, R. S., Bräutigam, K., Simillion, C., Dettmer, M. S., Vassella, E., Thirlwell, C., Perren, A., Marinoni, I.. 2020-04-08. Epigenetic landscape of pancreatic neuroendocrine tumours reveals distinct cells of origin and means of tumour progression. https://doi.org/10.1101/2020.04.08.029785

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