ArticleEpigenetics2012
DNA methylation analyses of urothelial carcinoma reveal distinct epigenetic subtypes and an association between gene copy number and methylation status.
Article in Epigenetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Epigenomic alterations in breast carcinoma from primary tumor to locoregional recurrences.PloS one · 2014Trial
- HOXB4 Promotes Bladder Cancer Progression in Part Through Transcriptional Activation of Smoothened.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The urothelial gene regulatory network: understanding biology to improve bladder cancer management.Oncogene · 2024Review
- Tumor purity adjusted beta values improve biological interpretability of high-dimensional DNA methylation data.PloS one · 2022Article
- SLC14A1 prevents oncometabolite accumulation and recruits HDAC1 to transrepress oncometabolite genes in urothelial carcinoma.Theranostics · 2020Article
- Article
- Epigenetic Alterations in Bladder Cancer.Current urology reports · 2018Review
- Integrative analysis of the epigenetic basis of muscle-invasive urothelial carcinoma.Clinical epigenetics · 2018Article
- HER2 and EGFR amplification and expression in urothelial carcinoma occurs in distinct biological and molecular contexts.Oncotarget · 2017Article
- PTTG1 regulated by miR-146a-3p promotes bladder cancer migration, invasion, metastasis and growth.Oncotarget · 2017Article
- DNA Methylation and Urological Cancer, a Step Towards Personalized Medicine: Current and Future Prospects.Molecular diagnosis & therapy · 2016Review
- Quantitative genome-wide methylation analysis of high-grade non-muscle invasive bladder cancer.Epigenetics · 2016Article
- An integrated genomics analysis of epigenetic subtypes in human breast tumors links DNA methylation patterns to chromatin states in normal mammary cells.Breast cancer research : BCR · 2016Article
- Bladder Cancer Molecular Taxonomy: Summary from a Consensus Meeting.Bladder cancer (Amsterdam, Netherlands) · 2016Article
- Uropathogenic E. coli (UPEC) Infection Induces Proliferation through Enhancer of Zeste Homologue 2 (EZH2).PloS one · 2016Article
- DNA methylation subgroups in melanoma are associated with proliferative and immunological processes.BMC medical genomics · 2015Article
- Changes in correlation between promoter methylation and gene expression in cancer.BMC genomics · 2015Article
- Genome methylation patterns in male breast cancer - Identification of an epitype with hypermethylation of polycomb target genes.Molecular oncology · 2015Article
- Genome-Wide DNA Methylation Analysis in Melanoma Reveals the Importance of CpG Methylation in MITF Regulation.The Journal of investigative dermatology · 2015Article
- [Epigenetics in urothelial cancer: Pathogenesis, improving diagnostics and developing novel treatment options].Der Urologe. Ausg. A · 2015Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We assessed DNA methylation and copy number status of 27,000 CpGs in 149 urothelial carcinomas and integrated the findings with gene expression and mutation data. Methylation was associated with gene expression for 1,332 CpGs, of which 26% showed positive correlation with expression, i.e., high methylation and high gene expression levels. These positively correlated CpGs were part of specific transcription factor binding sites, such as sites for MYC and CREBP1, or located in gene bodies. Furthermore, we found genes with copy number gains, low expression and high methylation levels, revealing an association between methylation and copy number levels. This phenomenon was typically observed for developmental genes, such as HOX genes, and tumor suppressor genes. In contrast, we also identified genes with copy number gains, high expression and low methylation levels. This was for instance observed for some keratin genes. Tumor cases could be grouped into four subgroups, termed epitypes, by their DNA methylation profiles. One epitype was influenced by the presence of infiltrating immune cells, two epitypes were mainly composed of non-muscle invasive tumors, and the remaining epitype of muscle invasive tumors. The polycomb complex protein EZH2 that blocks differentiation in embryonic stem cells showed increased expression both at the mRNA and protein levels in the muscle invasive epitype, together with methylation of polycomb target genes and HOX genes. Our data highlights HOX gene silencing and EZH2 expression as mechanisms to promote a more undifferentiated and aggressive state in UC.
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