Epigenetic landscape of pancreatic neuroendocrine tumours reveals distinct cells of origin and means of tumour progression.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
07 12 2020
07 12 2020
Historique:
received:
17
04
2020
accepted:
12
11
2020
entrez:
8
12
2020
pubmed:
9
12
2020
medline:
30
6
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33288854
doi: 10.1038/s42003-020-01479-y
pii: 10.1038/s42003-020-01479-y
pmc: PMC7721725
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
740Subventions
Organisme : Swiss National Science Foundation
ID : PMPDP3_164484
Pays : Switzerland
Organisme : Cancer Research UK
Pays : United Kingdom
Références
Nat Med. 2019 Aug;25(8):1260-1265
pubmed: 31263286
J Clin Endocrinol Metab. 2015 May;100(5):E776-82
pubmed: 25763608
Cell. 2013 Nov 7;155(4):934-47
pubmed: 24119843
Nature. 2017 Jul 19;547(7663):311-317
pubmed: 28726821
Gut. 2020 May;69(5):877-887
pubmed: 31462556
Gastroenterology. 2010 May;138(5):1954-65
pubmed: 20138042
Cell Rep. 2018 Jun 12;23(11):3407-3418
pubmed: 29898408
Nat Commun. 2013;4:2810
pubmed: 24326773
Genes (Basel). 2015 Oct 21;6(4):1053-75
pubmed: 26506390
Cell Syst. 2016 Oct 26;3(4):385-394.e3
pubmed: 27693023
Nat Genet. 2018 Jul;50(7):979-989
pubmed: 29915428
Cancer Discov. 2015 Dec;5(12):1296-313
pubmed: 26446169
Bioinformatics. 2013 Jan 15;29(2):189-96
pubmed: 23175756
Bioinformatics. 2012 Mar 15;28(6):882-3
pubmed: 22257669
Nature. 2017 Mar 2;543(7643):65-71
pubmed: 28199314
Nature. 2014 Jun 26;510(7506):537-41
pubmed: 24847876
BMC Bioinformatics. 2012 May 08;13:86
pubmed: 22568884
PLoS Comput Biol. 2013;9(8):e1003118
pubmed: 23950696
Bioinformatics. 2014 May 15;30(10):1363-9
pubmed: 24478339
Nature. 2010 Apr 22;464(7292):1149-54
pubmed: 20364121
Nature. 2011 Jan 20;469(7330):314-22
pubmed: 21248838
NPJ Genom Med. 2018 Jul 20;3:18
pubmed: 30062048
Biostatistics. 2007 Jan;8(1):118-27
pubmed: 16632515
Neuroendocrinology. 2016;103(2):153-71
pubmed: 26742109
Methods. 2010 Nov;52(3):248-54
pubmed: 20434562
Ann Surg. 2020 Mar;271(3):566-573
pubmed: 30339629
Endocr Relat Cancer. 2017 Sep;24(9):R315-R334
pubmed: 28710117
Cell Stem Cell. 2018 Jan 4;22(1):78-90.e4
pubmed: 29304344
Bioinformatics. 2010 Jun 15;26(12):1572-3
pubmed: 20427518
Bioinformatics. 2013 Oct 1;29(19):2519-20
pubmed: 23933972
Gastroenterology. 2014 Feb;146(2):453-60.e5
pubmed: 24148618
Epigenetics Chromatin. 2015 Jan 27;8:6
pubmed: 25972926
Diabetes. 2013 Oct;62(10):3514-22
pubmed: 23630303
Development. 1995 Jan;121(1):11-8
pubmed: 7867492
Endocr Relat Cancer. 2015 Jun;22(3):L13-8
pubmed: 25900181
Endocrinology. 2010 Aug;151(8):4024-30
pubmed: 20555035
Cancer Cell. 2016 Nov 14;30(5):806-821
pubmed: 27846393
Nat Commun. 2018 Oct 12;9(1):4158
pubmed: 30315258
PLoS One. 2012;7(7):e41361
pubmed: 22848472
J Clin Endocrinol Metab. 2007 Mar;92(3):1118-28
pubmed: 17179192
Bioinformatics. 2019 Feb 1;35(3):526-528
pubmed: 30016406
Cancer Cell. 2012 Oct 16;22(4):425-37
pubmed: 23079654
Nature. 2015 Feb 19;518(7539):317-30
pubmed: 25693563
Nature. 2018 Mar 22;555(7697):469-474
pubmed: 29539639
Bioinformatics. 2014 Feb 01;30(3):428-30
pubmed: 24336642
Cell. 2016 Jan 28;164(3):550-63
pubmed: 26824661
J Diabetes Res. 2019 Mar 13;2019:2583047
pubmed: 31001561
Eur J Cancer. 2012 Jul;48(11):1608-15
pubmed: 22129889
Semin Cell Dev Biol. 2015 Aug;44:107-14
pubmed: 26319183
Nat Commun. 2017 Nov 6;8(1):1323
pubmed: 29109526
Cancer Inform. 2014 Dec 09;13(Suppl 4):53-64
pubmed: 25574126
Development. 2018 May 14;145(10):
pubmed: 29759978
Nat Methods. 2014 Nov;11(11):1138-1140
pubmed: 25262207
Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14659-64
pubmed: 16195383
Genome Res. 2012 Feb;22(2):407-19
pubmed: 21613409
J Clin Invest. 2013 Mar;123(3):1275-84
pubmed: 23434589
Stat Appl Genet Mol Biol. 2004;3:Article3
pubmed: 16646809
Cell Metab. 2016 Oct 11;24(4):593-607
pubmed: 27667667
Nature. 2010 Dec 23;468(7327):1095-9
pubmed: 21150899
Cancer Res. 2016 Sep 15;76(18):5395-404
pubmed: 27496707
Hum Pathol. 2016 Oct;56:93-100
pubmed: 27342911
Elife. 2018 Feb 07;7:
pubmed: 29412141
Genome Biol. 2012 Jun 15;13(6):R44
pubmed: 22703947
Nature. 2019 May;569(7757):576-580
pubmed: 31092926
Endocr Pathol. 2020 Jun;31(2):108-118
pubmed: 32103422
Cell Metab. 2017 Mar 7;25(3):622-634
pubmed: 28215845
Nucleic Acids Res. 2017 Feb 28;45(4):e22
pubmed: 27924034