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5-Carboxylcytosine levels are elevated in human breast cancers and gliomas
BACKGROUND: DNA methylation (5-methylcytosine (5mC)) patterns are often altered in cancers. Ten-eleven translocation (Tet) proteins oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). In addition to their presumptive specific biological roles, these o...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546187/ https://www.ncbi.nlm.nih.gov/pubmed/26300993 http://dx.doi.org/10.1186/s13148-015-0117-x |
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author | Eleftheriou, Maria Pascual, Ana Jimenez Wheldon, Lee M. Perry, Christina Abakir, Abdulkadir Arora, Arvind Johnson, Andrew D. Auer, Dorothee T. Ellis, Ian O. Madhusudan, Srinivasan Ruzov, Alexey |
author_facet | Eleftheriou, Maria Pascual, Ana Jimenez Wheldon, Lee M. Perry, Christina Abakir, Abdulkadir Arora, Arvind Johnson, Andrew D. Auer, Dorothee T. Ellis, Ian O. Madhusudan, Srinivasan Ruzov, Alexey |
author_sort | Eleftheriou, Maria |
collection | PubMed |
description | BACKGROUND: DNA methylation (5-methylcytosine (5mC)) patterns are often altered in cancers. Ten-eleven translocation (Tet) proteins oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). In addition to their presumptive specific biological roles, these oxidised forms of 5mC may serve as intermediates in demethylation process. According to several reports, 5hmC levels are strongly decreased in cancers; however, the distribution of 5fC and 5caC in malignant tissue has not been studied. FINDINGS: Here, we examine the levels of 5hmC and 5caC in 28 samples of normal breast tissue, 59 samples of invasive human breast cancer and 74 samples of gliomas using immunochemistry. In agreement with previous reports, we show that 71 % of normal breast samples exhibit strong 5hmC signal, compared with only 18 % of breast cancer samples with equivalent levels of 5hmC staining. Unexpectedly, although 5caC is not detectable in normal breast tissue, 27 % of breast cancer samples exhibit significant staining for this modification (p < 0.001). Surprisingly, the presence of immunochemically detectable 5caC is not associated with the intensity of 5hmC signal in breast cancer tissue. In gliomas, we show that 5caC is detectable in 45 % of tumours. CONCLUSIONS: We demonstrate that, unlike 5hmC, the levels of 5caC are elevated in a proportion of breast cancers and gliomas. Our results reveal another level of complexity to the cancer epigenome, suggesting that active demethylation and/or 5caC-dependent transcriptional regulation are pre-activated in some tumours and may contribute to their pathogenesis. Larger studies to evaluate the clinicopathological significance of 5caC in cancers are warranted. |
format | Online Article Text |
id | pubmed-4546187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-45461872015-08-23 5-Carboxylcytosine levels are elevated in human breast cancers and gliomas Eleftheriou, Maria Pascual, Ana Jimenez Wheldon, Lee M. Perry, Christina Abakir, Abdulkadir Arora, Arvind Johnson, Andrew D. Auer, Dorothee T. Ellis, Ian O. Madhusudan, Srinivasan Ruzov, Alexey Clin Epigenetics Short Report BACKGROUND: DNA methylation (5-methylcytosine (5mC)) patterns are often altered in cancers. Ten-eleven translocation (Tet) proteins oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). In addition to their presumptive specific biological roles, these oxidised forms of 5mC may serve as intermediates in demethylation process. According to several reports, 5hmC levels are strongly decreased in cancers; however, the distribution of 5fC and 5caC in malignant tissue has not been studied. FINDINGS: Here, we examine the levels of 5hmC and 5caC in 28 samples of normal breast tissue, 59 samples of invasive human breast cancer and 74 samples of gliomas using immunochemistry. In agreement with previous reports, we show that 71 % of normal breast samples exhibit strong 5hmC signal, compared with only 18 % of breast cancer samples with equivalent levels of 5hmC staining. Unexpectedly, although 5caC is not detectable in normal breast tissue, 27 % of breast cancer samples exhibit significant staining for this modification (p < 0.001). Surprisingly, the presence of immunochemically detectable 5caC is not associated with the intensity of 5hmC signal in breast cancer tissue. In gliomas, we show that 5caC is detectable in 45 % of tumours. CONCLUSIONS: We demonstrate that, unlike 5hmC, the levels of 5caC are elevated in a proportion of breast cancers and gliomas. Our results reveal another level of complexity to the cancer epigenome, suggesting that active demethylation and/or 5caC-dependent transcriptional regulation are pre-activated in some tumours and may contribute to their pathogenesis. Larger studies to evaluate the clinicopathological significance of 5caC in cancers are warranted. BioMed Central 2015-08-21 /pmc/articles/PMC4546187/ /pubmed/26300993 http://dx.doi.org/10.1186/s13148-015-0117-x Text en © Eleftheriou et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Short Report Eleftheriou, Maria Pascual, Ana Jimenez Wheldon, Lee M. Perry, Christina Abakir, Abdulkadir Arora, Arvind Johnson, Andrew D. Auer, Dorothee T. Ellis, Ian O. Madhusudan, Srinivasan Ruzov, Alexey 5-Carboxylcytosine levels are elevated in human breast cancers and gliomas |
title | 5-Carboxylcytosine levels are elevated in human breast cancers and gliomas |
title_full | 5-Carboxylcytosine levels are elevated in human breast cancers and gliomas |
title_fullStr | 5-Carboxylcytosine levels are elevated in human breast cancers and gliomas |
title_full_unstemmed | 5-Carboxylcytosine levels are elevated in human breast cancers and gliomas |
title_short | 5-Carboxylcytosine levels are elevated in human breast cancers and gliomas |
title_sort | 5-carboxylcytosine levels are elevated in human breast cancers and gliomas |
topic | Short Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546187/ https://www.ncbi.nlm.nih.gov/pubmed/26300993 http://dx.doi.org/10.1186/s13148-015-0117-x |
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