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

Di Domenico, Annunziata; Pipinikas, Christodoulos P; Maire, Renaud S; Bräutigam, Konstantin; Simillion, Cedric; Dettmer, Matthias S; Vassella, Erik; Thirlwell, Chrissie; Perren, Aurel; Marinoni, Ilaria (2020). Epigenetic landscape of pancreatic neuroendocrine tumours reveals distinct cells of origin and means of tumour progression. Communications biology, 3(1), p. 740. Springer Nature 10.1038/s42003-020-01479-y

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Recent data suggest that Pancreatic Neuroendocrine Tumours (PanNETs) originate from α- or β-cells of the islets of Langerhans. The majority of PanNETs are non-functional and do not express cell-type specific hormones. In the current study we examine whether tumour DNA methylation (DNAme) profiling combined with genomic data is able to identify cell of origin and to reveal pathways involved in PanNET progression. We analyse genome-wide DNAme data of 125 PanNETs and sorted α- and β-cells. To confirm cell identity, we investigate ARX and PDX1 expression. Based on epigenetic similarities, PanNETs cluster in α-like, β-like and intermediate tumours. The epigenetic similarity to α-cells progressively decreases in the intermediate tumours, which present unclear differentiation. Specific transcription factor methylation and expression vary in the respective α/β-tumour groups. Depending on DNAme similarity to α/β-cells, PanNETs have different mutational spectra, stage of the disease and prognosis, indicating potential means of PanNET progression.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Tissue Bank Bern
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Translational Research Unit

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Di Domenico, Annunziata; Maire, Renaud Sylvain; Bräutigam, Konstantin; Dettmer, Matthias S; Vassella, Erik; Perren, Aurel and Marinoni, Ilaria

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2399-3642

Publisher:

Springer Nature

Language:

English

Submitter:

Aurel Perren

Date Deposited:

21 Jan 2021 09:15

Last Modified:

24 Jan 2021 03:00

Publisher DOI:

10.1038/s42003-020-01479-y

PubMed ID:

33288854

BORIS DOI:

10.7892/boris.150435

URI:

https://boris.unibe.ch/id/eprint/150435

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