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Medulloblastoma and ependymoma cells display increased levels of 5-carboxylcytosine and elevated TET1 expression

Overview of attention for article published in Clinical Epigenetics, February 2017
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Title
Medulloblastoma and ependymoma cells display increased levels of 5-carboxylcytosine and elevated TET1 expression
Published in
Clinical Epigenetics, February 2017
DOI 10.1186/s13148-016-0306-2
Pubmed ID
Authors

Ashley Ramsawhook, Lara Lewis, Beth Coyle, Alexey Ruzov

Abstract

Alteration of DNA methylation (5-methylcytosine, 5mC) patterns represents one of the causes of tumorigenesis and cancer progression. Tet proteins can oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine (5caC). Although the roles of these oxidised forms of 5mC (oxi-mCs) in cancer pathogenesis are still largely unknown, there are indications that they may be involved in the mechanisms of malignant transformation. Thus, reduction of 5hmC content represents an epigenetic hallmark of human tumours, and according to our recent report, 5caC is enriched in a proportion of breast cancers and gliomas. Nevertheless, the distribution of oxi-mCs in paediatric brain tumours has not been assessed. Here, we analyse the global levels and spatial distribution of 5hmC and 5caC in four brain tumour cell lines derived from paediatric sonic hedgehog (SHH) pathway-activated medulloblastomas (Daoy and UW228-3) and ependymomas (BXD-1425EPN and DKFZ-EP1NS). We show that, unlike HeLa cells, the paediatric tumour cell lines possess both 5hmC and 5caC at immunochemically detectable levels and demonstrate that both modifications display high degrees of spatial overlap in the nuclei of medulloblastomas and ependymomas. Moreover, although 5hmC levels are comparable in the four brain tumour cell lines, 5caC staining intensities differ dramatically between them with highest levels of this mark in a subpopulation of DKFZ-EP1NS cells. Remarkably, the 5caC enrichment does not correlate with 5hmC levels and is not associated with alterations in thymine DNA glycosylase (TDG) expression in SHH medulloblastoma and ependymoma cell lines but corresponds to elevated levels of TET1 transcript in UW228-3 and DKFZ-EP1NS cells. We demonstrate that both 5caC enrichment and elevated TET1 expression are observed in SHH medulloblastomas and ependymomas. Our results suggest that increased Tet-dependent 5mC oxidation may represent one of the epigenetic signatures of cancers with neural stem cell origin and, thus, may contribute to development of novel approaches for diagnosis and therapy of the brain tumours.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 21 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 6 29%
Student > Ph. D. Student 3 14%
Student > Master 3 14%
Researcher 2 10%
Professor 1 5%
Other 2 10%
Unknown 4 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 33%
Medicine and Dentistry 5 24%
Agricultural and Biological Sciences 2 10%
Neuroscience 1 5%
Chemistry 1 5%
Other 0 0%
Unknown 5 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 February 2017.
All research outputs
#4,951,138
of 9,107,880 outputs
Outputs from Clinical Epigenetics
#356
of 477 outputs
Outputs of similar age
#179,015
of 316,097 outputs
Outputs of similar age from Clinical Epigenetics
#13
of 20 outputs
Altmetric has tracked 9,107,880 research outputs across all sources so far. This one is in the 27th percentile – i.e., 27% of other outputs scored the same or lower than it.
So far Altmetric has tracked 477 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.4. This one is in the 19th percentile – i.e., 19% of its peers scored the same or lower than it.
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We're also able to compare this research output to 20 others from the same source and published within six weeks on either side of this one. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.