5-Hydroxymethylcytosine: An epigenetic mark frequently deregulated in cancer

Kroeze, Leonie I.; Reijden, Bert A. van der; Jansen, Joop H.

doi:10.1016/j.bbcan.2015.01.001

Cited by 80 publications

(82 citation statements)

References 150 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TET proteins catalyze the conversion of the 5-methylcytosine into 5-hydroxymethylcytosine (5-hmC), and further to 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC), which initiates the process of DNA demethylation. [8][9][10] To date, a number of studies confirmed the important role of TET proteins in the DNA demethylation and their relationship with changes in DNA methylation pattern in tumors. TET proteins seem to be also involved in the regulation of other epigenetic modifications, that is, the modification of histones by interacting with specific proteins responsible for these modifications and their recruitment to chromatin.…”

Section: Introductionmentioning

confidence: 97%

Differential expression of ten-eleven translocation genes in endometrial cancers

et al. 2017

View full text Add to dashboard Cite

Ten-eleven translocation proteins are α-ketoglutarate-dependent dioxygenases involved in the conversion of 5-methylcytosines (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine, and 5-carboxylcytosine that play a significant role in DNA demethylation. Deregulation of TET genes expression and changes in the level of 5-hmC are thought to be associated with the onset and progression of several types of cancer, but there are no such data related to endometrial cancer. The aim of the work was to investigate the messenger RNA expression levels of TET1, TET2, and TET3 in relation to clinicopathological characteristics of endometrial cancer as well as the correlation between expression of TET genes and the level of 5-hmC/5-mC. The prognostic significance of TETs expression for overall survival was established. We found that TET1 and TET2 messenger RNA expression was lower and TET3 was higher in cancers compared to normal tissues. Positive correlation between 5-hmC and the relative expression of TET1 and TET2 was found, but no correlation was observed in the case of TET3. Decreased expression of TET1 and TET2 was significantly associated with increased lymph node metastasis and International Federation of Gynecology and Obstetrics stage. Kaplan-Meier analysis indicated that low TET1 expression predicted poor overall survival (p = 0.038). Multivariate analysis identified the TET1 expression in endometrial cancer as an independent prognostic factor. Our results suggest that decreased expression of TET1 correlates with tumor progression and may serve as a potential prognostic biomarker in endometrial cancer.

show abstract

Section: Introductionmentioning

confidence: 97%

Differential expression of ten-eleven translocation genes in endometrial cancers

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Invariably reduced levels of 5hmC have been reported in tumors of the lung, colon, brain, breast, liver, prostate, kidney, melanoma, etc, compared to its respective normal tissues [21][22][23]. This loss of 5hmC in genomic context may lead to gene body hypermethylation as observed in kidney cancer and can hypermethylate promoters of tumor suppressor genes (TSG) that are frequently observed in cancers [24].…”

Section: Interplay Between 5-hydroxymethylcytosine and Cancermentioning

confidence: 99%

Regulation and Functional Significance of 5-Hydroxymethylcytosine in Cancer

et al. 2017

View full text Add to dashboard Cite

Epigenetic modes of gene regulation are important for physiological conditions and its aberrant changes can lead to disease like cancer. 5-hydroxymethylcytosine (5hmC) is an oxidized form of 5-methylcytosine (5mC) catalyzed by Ten Eleven Translocation (TET) enzymes. 5hmC is considered to be a demethylation intermediate and is emerging as a stable and functional base modification. The global loss of 5hmC level is commonly observed in cancers and tumorigenic germline mutations in IDH, SDH and FH are found to be inhibiting TET activity. Although a global loss of 5hmC is characteristic in cancers, locus-specific 5hmC gain implicates selective gene expression control. The definitive role of 5hmC as a tumor suppressing or promoting modification can be deduced by identifying locus-specific 5hmC modification in different types of cancer. Determining the genes carrying 5hmC modifications and its selective variation will open up new therapeutic targets. This review outlines the role of global and locus-specific changes of 5hmC in cancers and the possible mechanisms underlying such changes. We have described major cellular factors that influence 5hmC levels and highlighted the significance of 5hmC in tumor micro environmental condition like hypoxia.

show abstract

“…Thus, our data suggest that 5-hmC homeostasis is dynamic and an independent epigenetic marker. Accordingly, other studies showed that, beyond being a transient intermediate, 5-hmC is directly involved in the regulation of gene expression and transcription [22][23][24] . Decreased global levels of 5-hmC and unchanged 5-mC levels were observed in multiple cancers, including colon, prostate, and breast cancers [25] .…”

Section: Color Version Available Onlinementioning

confidence: 99%

Altered Global 5-Hydroxymethylation Status in Hidradenitis Suppurativa: Support for an Epigenetic Background

Hessam

Sand²,

Lang³

et al. 2017

Dermatology

View full text Add to dashboard Cite

Background: The pathogenesis of hidradenitis suppurativa (HS), with its complex inflammatory network, is still elusive. Imbalances in DNA methylation can lead to genome destabilization and have been assumed to play a role in inflammatory diseases. Global DNA methylation and hydroxymethylation have not been studied in HS yet. Objective: We conducted this study to investigate the global DNA methylation and hydroxymethylation status in lesional and perilesional HS skin compared to healthy controls. Methods: Immunohistochemical analysis was performed for 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in 30 lesional and 30 corresponding healthy-appearing perilesional HS tissue samples. We included 30 healthy subjects as an interindividual control group. Results: 5-hmC levels were significantly lower in healthy-appearing perilesional (p < 0.0001) and lesional HS skin (p < 0.0001) when compared to healthy controls. There was no significant difference between lesional HS skin and perilesional HS skin regarding 5-hmC levels (p = 0.6654). In contrast to 5-hmC, 5-mC staining showed no significant changes between the 3 groups. Univariate analysis revealed no significant association between patients' characteristics, disease severity, and the levels of 5-mC and 5-hmC. Conclusion: Our findings indicate that imbalances in DNA hydroxymethylation may play a role in the pathogenesis of HS rather than DNA methylation. Further studies are warranted to investigate the significance of DNA hydroxymethylation and the regulating enzymes in HS in order to advance our knowledge of the inflammatory network in this disease.

show abstract

5-Hydroxymethylcytosine: An epigenetic mark frequently deregulated in cancer

Cited by 80 publications

References 150 publications

Differential expression of ten-eleven translocation genes in endometrial cancers

Differential expression of ten-eleven translocation genes in endometrial cancers

Regulation and Functional Significance of 5-Hydroxymethylcytosine in Cancer

Altered Global 5-Hydroxymethylation Status in Hidradenitis Suppurativa: Support for an Epigenetic Background

Contact Info

Product

Resources

About