DNA Methylation Profiles of Ovarian Clear Cell Carcinoma.
Adenocarcinoma, Clear Cell
/ ethnology
Adult
Aged
Aged, 80 and over
Aneuploidy
Class I Phosphatidylinositol 3-Kinases
/ genetics
CpG Islands
/ genetics
DNA Methylation
DNA-Binding Proteins
/ genetics
Disease Progression
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Middle Aged
Mutation
Neoplasm Staging
Ovarian Neoplasms
/ ethnology
Prognosis
Transcription Factors
/ genetics
Tumor Suppressor Protein p53
/ genetics
Journal
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ISSN: 1538-7755
Titre abrégé: Cancer Epidemiol Biomarkers Prev
Pays: United States
ID NLM: 9200608
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
27
05
2021
revised:
18
08
2021
accepted:
21
10
2021
pubmed:
27
10
2021
medline:
12
3
2022
entrez:
26
10
2021
Statut:
ppublish
Résumé
Ovarian clear cell carcinoma (OCCC) is a rare ovarian cancer histotype that tends to be resistant to standard platinum-based chemotherapeutics. We sought to better understand the role of DNA methylation in clinical and biological subclassification of OCCC. We interrogated genome-wide methylation using DNA from fresh frozen tumors from 271 cases, applied nonsmooth nonnegative matrix factorization (nsNMF) clustering, and evaluated clinical associations and biological pathways. Two approximately equally sized clusters that associated with several clinical features were identified. Compared with Cluster 2 ( DNA methylation clusters in OCCC correlate with disease features and gene expression patterns among immune pathways. This work serves as a foundation for integrative analyses that better understand the complex biology of OCCC in an effort to improve potential for development of targeted therapeutics.
Sections du résumé
BACKGROUND
Ovarian clear cell carcinoma (OCCC) is a rare ovarian cancer histotype that tends to be resistant to standard platinum-based chemotherapeutics. We sought to better understand the role of DNA methylation in clinical and biological subclassification of OCCC.
METHODS
We interrogated genome-wide methylation using DNA from fresh frozen tumors from 271 cases, applied nonsmooth nonnegative matrix factorization (nsNMF) clustering, and evaluated clinical associations and biological pathways.
RESULTS
Two approximately equally sized clusters that associated with several clinical features were identified. Compared with Cluster 2 (
CONCLUSIONS
DNA methylation clusters in OCCC correlate with disease features and gene expression patterns among immune pathways.
IMPACT
This work serves as a foundation for integrative analyses that better understand the complex biology of OCCC in an effort to improve potential for development of targeted therapeutics.
Identifiants
pubmed: 34697060
pii: 1055-9965.EPI-21-0677
doi: 10.1158/1055-9965.EPI-21-0677
pmc: PMC8755592
mid: NIHMS1752802
doi:
Substances chimiques
ARID1A protein, human
0
DNA-Binding Proteins
0
TP53 protein, human
0
Transcription Factors
0
Tumor Suppressor Protein p53
0
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
132-141Subventions
Organisme : NCI NIH HHS
ID : P30 CA047904
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA228991
Pays : United States
Organisme : Cancer Research UK
ID : 15601
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA015083
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA248288
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA222867
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA136393
Pays : United States
Informations de copyright
©2021 American Association for Cancer Research.
Références
Biostatistics. 2007 Jan;8(1):118-27
pubmed: 16632515
BMC Cancer. 2018 Mar 27;18(1):347
pubmed: 29587661
Gynecol Oncol. 2012 Sep;126(3):481-90
pubmed: 22525820
Ann Oncol. 2013 Dec;24 Suppl 10:x16-21
pubmed: 24265397
J Clin Invest. 2020 May 1;130(5):2712-2726
pubmed: 32027624
JAMA Oncol. 2017 Dec 1;3(12):e173290
pubmed: 29049607
Nat Genet. 2019 May;51(5):815-823
pubmed: 31043753
Biopreserv Biobank. 2013 Apr;11(2):83-93
pubmed: 24845429
Bioinformatics. 2014 Apr 1;30(7):1015-6
pubmed: 24371154
Clin Cancer Res. 2019 Oct 1;25(19):5937-5946
pubmed: 31142506
Gynecol Oncol. 2018 Nov;151(2):381-389
pubmed: 30217369
N Engl J Med. 2010 Oct 14;363(16):1532-43
pubmed: 20942669
Int J Gynecol Cancer. 2021 Apr;31(4):605-616
pubmed: 32948640
J Gynecol Oncol. 2017 Nov;28(6):e77
pubmed: 29027395
Nat Genet. 2017 May;49(5):680-691
pubmed: 28346442
Healthcare (Basel). 2019 Jul 30;7(3):
pubmed: 31366141
EBioMedicine. 2019 Dec;50:203-210
pubmed: 31761620
Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4164-9
pubmed: 15016911
Nature. 1999 Oct 21;401(6755):788-91
pubmed: 10548103
Int J Mol Sci. 2013 Mar 06;14(3):5367-79
pubmed: 23466883
Hum Mol Genet. 2015 Jul 1;24(13):3595-607
pubmed: 25804953
Cancer Epidemiol Biomarkers Prev. 2013 Oct;22(10):1677-86
pubmed: 23880734
Nat Commun. 2013;4:1628
pubmed: 23535649
Clin Cancer Res. 2018 Feb 1;24(3):569-580
pubmed: 29061645
Mod Pathol. 2017 Feb;30(2):297-303
pubmed: 27767100
Future Oncol. 2015;11(9):1389-405
pubmed: 25952785
Genome Biol. 2010;11(2):R14
pubmed: 20132535
Sci Rep. 2020 May 14;10(1):7946
pubmed: 32409713
Genome Biol. 2016 Oct 7;17(1):208
pubmed: 27717381
JCI Insight. 2016 Aug 18;1(13):
pubmed: 27617304
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
BJOG. 2020 Oct;127(11):1409-1420
pubmed: 32285600
Clin Cancer Res. 2011 Apr 15;17(8):2538-48
pubmed: 21343371
Hum Mol Genet. 2013 Aug 1;22(15):3038-47
pubmed: 23571109
Science. 2010 Oct 8;330(6001):228-31
pubmed: 20826764
Cancer Discov. 2015 Jul;5(7):752-67
pubmed: 26069190
Am J Surg Pathol. 2020 May;44(5):649-656
pubmed: 32294063
J Pathol. 2015 Jun;236(2):201-9
pubmed: 25692284
Int J Oncol. 2012 Sep;41(3):1094-100
pubmed: 22751940
Int J Gynecol Cancer. 2016 May;26(4):648-54
pubmed: 26937756
IEEE Trans Pattern Anal Mach Intell. 2006 Mar;28(3):403-15
pubmed: 16526426
J Pathol. 2018 Apr;244(5):550-564
pubmed: 29344971
J Gynecol Oncol. 2016 May;27(3):e31
pubmed: 27029752