DNA Methylation Signatures and the Contribution of Age-Associated Methylomic Drift to Carcinogenesis in Early-Onset Colorectal Cancer.
DNA methylation
age acceleration
colorectal cancer
early onset colorectal cancer
epigenetic drift
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
25 May 2021
25 May 2021
Historique:
received:
16
04
2021
revised:
14
05
2021
accepted:
19
05
2021
entrez:
2
6
2021
pubmed:
3
6
2021
medline:
3
6
2021
Statut:
epublish
Résumé
We investigated aberrant DNA methylation (DNAm) changes and the contribution of ageing-associated methylomic drift and age acceleration to early-onset colorectal cancer (EOCRC) carcinogenesis. Genome-wide DNAm profiling using the Infinium HM450K on 97 EOCRC tumour and 54 normal colonic mucosa samples was compared with: (1) intermediate-onset CRC (IOCRC; diagnosed between 50-70 years; 343 tumour and 35 normal); and (2) late-onset CRC (LOCRC; >70 years; 318 tumour and 40 normal). CpGs associated with age-related methylation drift were identified using a public dataset of 231 normal mucosa samples from people without CRC. DNAm-age was estimated using epiTOC2. Common to all three age-of-onset groups, 88,385 (20% of all CpGs) CpGs were differentially methylated between tumour and normal mucosa. We identified 234 differentially methylated genes that were unique to the EOCRC group; 13 of these DMRs/genes were replicated in EOCRC compared with LOCRCs from TCGA. In normal mucosa from people without CRC, we identified 28,154 CpGs that undergo ageing-related DNAm drift, and of those, 65% were aberrantly methylated in EOCRC tumours. Based on the mitotic-based DNAm clock epiTOC2, we identified age acceleration in normal mucosa of people with EOCRC compared with normal mucosa from the IOCRC, LOCRC groups (
Identifiants
pubmed: 34070516
pii: cancers13112589
doi: 10.3390/cancers13112589
pmc: PMC8199056
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NCI NIH HHS
ID : U01 CA167551
Pays : United States
Références
Cancer Res. 1998 Dec 1;58(23):5489-94
pubmed: 9850084
Aging (Albany NY). 2018 Apr 18;10(4):573-591
pubmed: 29676998
Epigenetics Chromatin. 2015 Jan 27;8:6
pubmed: 25972926
Gastroenterol Rep (Oxf). 2014 Feb;2(1):16-20
pubmed: 24760232
Cancer Res. 2020 Feb 1;80(3):367-374
pubmed: 31694907
Int J Obes (Lond). 2019 Jan;43(1):176-188
pubmed: 29717273
Nucleic Acids Res. 2013 Apr;41(7):e90
pubmed: 23476028
J Gastroenterol Hepatol. 2015 Jan;30(1):6-13
pubmed: 25251195
Nat Genet. 2018 Apr;50(4):591-602
pubmed: 29610480
BMC Res Notes. 2015 Oct 06;8:543
pubmed: 26438025
Bioinformatics. 2012 Mar 15;28(6):882-3
pubmed: 22257669
Science. 2015 Jan 2;347(6217):78-81
pubmed: 25554788
Carcinogenesis. 2010 Jun;31(6):1158-63
pubmed: 20395289
Nucleic Acids Res. 2016 Feb 18;44(3):e20
pubmed: 26384415
Nat Rev Genet. 2018 Jun;19(6):371-384
pubmed: 29643443
Cold Spring Harb Perspect Biol. 2016 Sep 01;8(9):
pubmed: 27194046
J Clin Invest. 2014 Jan;124(1):24-9
pubmed: 24382386
Bioinformatics. 2014 May 15;30(10):1363-9
pubmed: 24478339
J Natl Cancer Inst. 2018 Jul 1;110(7):791-793
pubmed: 29370418
Genome Med. 2020 Jun 24;12(1):56
pubmed: 32580750
Nat Methods. 2018 Dec;15(12):1059-1066
pubmed: 30504870
Cancer Res. 2019 Feb 1;79(3):495-504
pubmed: 30291105
Clin Epigenetics. 2018 Oct 16;10(1):123
pubmed: 30326963
Genome Biol. 2016 Oct 3;17(1):205
pubmed: 27716309
Gut. 2018 Nov;67(11):1995-2005
pubmed: 28982739
Mol Cell. 2013 Jan 24;49(2):359-367
pubmed: 23177740
J Gastroenterol Hepatol. 2017 Feb;32(2):427-438
pubmed: 27273229
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Clin Epigenetics. 2015 Feb 20;7:12
pubmed: 25806089
Cancer Causes Control. 2013 Feb;24(2):335-41
pubmed: 23224326
Gastroenterology. 2018 Mar;154(4):897-905.e1
pubmed: 29146522
Genome Res. 2010 Mar;20(3):332-40
pubmed: 20107151
PLoS One. 2012;7(9):e45357
pubmed: 23049789
Epigenetics. 2013 Jul;8(7):748-55
pubmed: 23804018
BMC Bioinformatics. 2010 Nov 30;11:587
pubmed: 21118553
Lancet. 2014 Apr 26;383(9927):1490-1502
pubmed: 24225001
Int J Epidemiol. 2018 Apr 1;47(2):387-388i
pubmed: 29490034
Cancer Cell Int. 2017 Aug 7;17:75
pubmed: 28794688
Oncogene. 2018 Feb 1;37(5):566-577
pubmed: 28991233
Mayo Clin Proc. 2014 Feb;89(2):216-24
pubmed: 24393412
Bioinformatics. 2016 Jan 15;32(2):286-8
pubmed: 26424855
J Pediatr Endocrinol Metab. 2015 Mar;28(3-4):251-63
pubmed: 25581748
Nucleic Acids Res. 2016 May 5;44(8):e71
pubmed: 26704973
Clin Epigenetics. 2020 Jan 3;12(1):5
pubmed: 31900199
Genome Biol. 2014 Dec 03;15(12):503
pubmed: 25599564
JAMA Oncol. 2017 Apr 1;3(4):464-471
pubmed: 27978560
Cancer Epidemiol Biomarkers Prev. 2007 Nov;16(11):2331-43
pubmed: 17982118
J Clin Pathol. 2001 Jul;54(7):533-8
pubmed: 11429425
Int J Epidemiol. 2017 Dec 1;46(6):1757-1757i
pubmed: 28641380
Genome Biol. 2013;14(10):R115
pubmed: 24138928
J Natl Cancer Inst. 2014 Jun 28;106(7):
pubmed: 24973978
Science. 2018 Mar 23;359(6382):1376-1383
pubmed: 29519916
J Natl Cancer Inst. 2005 Sep 21;97(18):1330-8
pubmed: 16174854
Clin Gastroenterol Hepatol. 2020 Nov;18(12):2752-2759.e2
pubmed: 31622737
Am J Gastroenterol. 2011 Nov;106(11):1911-21; quiz 1922
pubmed: 21912438
Cancer Res. 2014 Mar 1;74(5):1475-83
pubmed: 24453003
PLoS One. 2014 Oct 06;9(10):e108668
pubmed: 25286412
Br J Cancer. 2018 Oct;119(7):785-792
pubmed: 30287914
Breast Cancer Res Treat. 2016 Nov;160(1):173-180
pubmed: 27604360
Am J Surg Pathol. 2013 Mar;37(3):399-405
pubmed: 23348208