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The DNA methylomes of serous borderline tumors reveal subgroups with malignant- or benign-like profiles.
- Source :
-
The American journal of pathology [Am J Pathol] 2013 Mar; Vol. 182 (3), pp. 668-77. Date of Electronic Publication: 2013 Jan 25. - Publication Year :
- 2013
-
Abstract
- Serous borderline tumors (SBOTs) are a challenging group of ovarian tumors positioned between benign and malignant disease. We have profiled the DNA methylomes of 12 low-grade serous carcinomas (LGSCs), 19 SBOTs, and 16 benign serous tumors (BSTs) across 27,578 CpG sites to further characterize the epigenomic relationship between these subtypes of ovarian tumors. Unsupervised hierarchical clustering of DNA methylation levels showed that LGSCs differ distinctly from BSTs, but not from SBOTs. Gene ontology analysis of genes showing differential methylation at linked CpG sites between LGSCs and BSTs revealed significant enrichment of gene groups associated with cell adhesion, cell-cell signaling, and the extracellular region, consistent with a more invasive phenotype of LGSCs compared with BSTs. Consensus clustering highlighted differences between SBOT methylomes and returned subgroups with malignant- or benign-like methylation profiles. Furthermore, a two-loci DNA methylation signature can distinguish between these SBOT subgroups with benign- and malignant-like methylation characteristics. Our findings indicate striking similarities between SBOT and LGSC methylomes, supporting a common origin and the view that LGSC may arise from SBOT. A subgroup of SBOTs can be classified into tumors with a benign- or a malignant-like methylation profile that may help in identifying tumors more likely to progress into LGSCs.<br /> (Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Cluster Analysis
CpG Islands genetics
Cystadenocarcinoma, Serous pathology
Female
Genes, Neoplasm genetics
Genetic Loci genetics
Humans
Middle Aged
Neoplasm Grading
Ovarian Neoplasms pathology
Principal Component Analysis
Young Adult
Cystadenocarcinoma, Serous classification
Cystadenocarcinoma, Serous genetics
DNA Methylation genetics
Ovarian Neoplasms classification
Ovarian Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1525-2191
- Volume :
- 182
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 23357500
- Full Text :
- https://doi.org/10.1016/j.ajpath.2012.11.040