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Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays
CpG island arrays represent a high-throughput epigenomic discovery platform to identify global disease-specific promoter hypermethylation candidates along bladder cancer progression. DNA obtained from 10 pairs of invasive bladder tumours were profiled vs their respective normal urothelium using diff...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361432/ https://www.ncbi.nlm.nih.gov/pubmed/18087279 http://dx.doi.org/10.1038/sj.bjc.6604143 |
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author | Aleman, A Adrien, L Lopez-Serra, L Cordon-Cardo, C Esteller, M Belbin, T J Sanchez-Carbayo, M |
author_facet | Aleman, A Adrien, L Lopez-Serra, L Cordon-Cardo, C Esteller, M Belbin, T J Sanchez-Carbayo, M |
author_sort | Aleman, A |
collection | PubMed |
description | CpG island arrays represent a high-throughput epigenomic discovery platform to identify global disease-specific promoter hypermethylation candidates along bladder cancer progression. DNA obtained from 10 pairs of invasive bladder tumours were profiled vs their respective normal urothelium using differential methylation hybridisation on custom-made CpG arrays (n=12 288 clones). Promoter hypermethylation of 84 clones was simultaneously shown in at least 70% of the tumours. SOX9 was selected for further validation by bisulphite genomic sequencing and methylation-specific polymerase chain reaction in bladder cancer cells (n=11) and primary bladder tumours (n=101). Hypermethylation was observed in bladder cancer cells and associated with lack of gene expression, being restored in vitro by a demethylating agent. In primary bladder tumours, SOX9 hypermethylation was present in 56.4% of the cases. Moreover, SOX9 hypermethylation was significantly associated with tumour grade and overall survival. Thus, this high-throughput epigenomic strategy has served to identify novel hypermethylated candidates in bladder cancer. In vitro analyses supported the role of methylation in silencing SOX9 gene. The association of SOX9 hypermethylation with tumour progression and clinical outcome suggests its relevant clinical implications at stratifying patients affected with bladder cancer. |
format | Text |
id | pubmed-2361432 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23614322009-09-10 Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays Aleman, A Adrien, L Lopez-Serra, L Cordon-Cardo, C Esteller, M Belbin, T J Sanchez-Carbayo, M Br J Cancer Molecular Diagnostics CpG island arrays represent a high-throughput epigenomic discovery platform to identify global disease-specific promoter hypermethylation candidates along bladder cancer progression. DNA obtained from 10 pairs of invasive bladder tumours were profiled vs their respective normal urothelium using differential methylation hybridisation on custom-made CpG arrays (n=12 288 clones). Promoter hypermethylation of 84 clones was simultaneously shown in at least 70% of the tumours. SOX9 was selected for further validation by bisulphite genomic sequencing and methylation-specific polymerase chain reaction in bladder cancer cells (n=11) and primary bladder tumours (n=101). Hypermethylation was observed in bladder cancer cells and associated with lack of gene expression, being restored in vitro by a demethylating agent. In primary bladder tumours, SOX9 hypermethylation was present in 56.4% of the cases. Moreover, SOX9 hypermethylation was significantly associated with tumour grade and overall survival. Thus, this high-throughput epigenomic strategy has served to identify novel hypermethylated candidates in bladder cancer. In vitro analyses supported the role of methylation in silencing SOX9 gene. The association of SOX9 hypermethylation with tumour progression and clinical outcome suggests its relevant clinical implications at stratifying patients affected with bladder cancer. Nature Publishing Group 2008-01-29 2007-12-18 /pmc/articles/PMC2361432/ /pubmed/18087279 http://dx.doi.org/10.1038/sj.bjc.6604143 Text en Copyright © 2008 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Molecular Diagnostics Aleman, A Adrien, L Lopez-Serra, L Cordon-Cardo, C Esteller, M Belbin, T J Sanchez-Carbayo, M Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays |
title | Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays |
title_full | Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays |
title_fullStr | Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays |
title_full_unstemmed | Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays |
title_short | Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays |
title_sort | identification of dna hypermethylation of sox9 in association with bladder cancer progression using cpg microarrays |
topic | Molecular Diagnostics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361432/ https://www.ncbi.nlm.nih.gov/pubmed/18087279 http://dx.doi.org/10.1038/sj.bjc.6604143 |
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