DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
03 02 2021
03 02 2021
Historique:
received:
29
04
2020
accepted:
02
11
2020
entrez:
4
2
2021
pubmed:
5
2
2021
medline:
10
8
2021
Statut:
epublish
Résumé
Here we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs.
Identifiants
pubmed: 33536587
doi: 10.1038/s42003-020-01469-0
pii: 10.1038/s42003-020-01469-0
pmc: PMC7859232
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
155Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : U54 HG003273
Pays : United States
Organisme : Cancer Research UK
ID : C29717/A17263
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C29717/A18484
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C596/A18076
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C596/A20921
Pays : United Kingdom
Investigateurs
Maria Scardoni
(M)
Claudio Bassi
(C)
Sonia Grimaldi
(S)
Cinzia Cantù
(C)
Giada Bonizzato
(G)
Samantha Bersani
(S)
Davide Antonello
(D)
Liliana Piredda
(L)
Nicola Sperandio
(N)
Stefano Barbi
(S)
Paola Merlini
(P)
Références
Science. 2011 Mar 4;331(6021):1199-203
pubmed: 21252315
Proc Natl Acad Sci U S A. 2017 Dec 19;114(51):13525-13530
pubmed: 29203669
Nat Med. 2019 Aug;25(8):1260-1265
pubmed: 31263286
PLoS One. 2009 Dec 18;4(12):e8274
pubmed: 20019873
Endocr Rev. 2019 Apr 1;40(2):506-536
pubmed: 30657883
Bioinformatics. 2014 Feb 01;30(3):428-30
pubmed: 24336642
Ann Surg. 2003 Sep;238(3):423-31; discussion 431-2
pubmed: 14501508
Endocr Relat Cancer. 2016 Aug;23(8):625-33
pubmed: 27353036
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Cell Syst. 2016 Oct 26;3(4):385-394.e3
pubmed: 27693023
Eur J Gastroenterol Hepatol. 2017 Jul;29(7):826-830
pubmed: 28328619
PLoS Genet. 2010 Apr 22;6(4):e1000917
pubmed: 20421991
Nature. 2010 Jul 8;466(7303):253-7
pubmed: 20613842
Commun Biol. 2020 Dec 7;3(1):740
pubmed: 33288854
Bioinformatics. 2013 Jan 15;29(2):189-96
pubmed: 23175756
Nature. 2017 Mar 2;543(7643):65-71
pubmed: 28199314
Clin Cancer Res. 2017 Jan 15;23(2):600-609
pubmed: 27407094
Bioinformatics. 2012 Jun 1;28(11):1530-2
pubmed: 22539670
Neuroendocrinology. 2014;100(1):26-34
pubmed: 25011998
Endocr Relat Cancer. 2017 Mar;24(3):137-146
pubmed: 28115389
Bioinformatics. 2014 May 15;30(10):1363-9
pubmed: 24478339
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
Dig Liver Dis. 2019 Apr;51(4):595-599
pubmed: 30824408
Ann Surg. 2020 Mar;271(3):566-573
pubmed: 30339629
Nat Commun. 2018 Oct 12;9(1):4158
pubmed: 30315258
Endocr Relat Cancer. 2019 Aug 1;26(9):R519-R544
pubmed: 31252410
Genome Biol. 2010;11(3):R25
pubmed: 20196867
Cancer. 2019 Apr 15;125(8):1247-1257
pubmed: 30620390
Cancers (Basel). 2020 Jun 04;12(6):
pubmed: 32512761
BMC Bioinformatics. 2011 Aug 04;12:323
pubmed: 21816040
Endocrinol Metab Clin North Am. 2011 Mar;40(1):1-18, vii
pubmed: 21349409
Nature. 2012 Nov 15;491(7424):399-405
pubmed: 23103869
Cancer Res. 2017 Feb 15;77(4):823-826
pubmed: 28159862
Cancer Cell. 2014 Oct 13;26(4):577-90
pubmed: 25263941
J Biol Chem. 1994 Jun 24;269(25):17228-37
pubmed: 8006031
Eur J Endocrinol. 2018 Sep;179(3):153-160
pubmed: 29903750
Gastroenterology. 2018 Jun;154(8):2060-2063.e8
pubmed: 29486199
Genome Biol. 2013 Sep 24;14(9):r105
pubmed: 24063430
Mol Cancer Ther. 2014 May;13(5):1334-44
pubmed: 24568970
Nucleic Acids Res. 2017 Feb 28;45(4):e22
pubmed: 27924034
Endocr Connect. 2019 Jul;8(7):1052-1060
pubmed: 31252400