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Promoter hypermethylation profiling of distant breast cancer metastases

Promoter hypermethylation of tumor suppressor genes seems to be an early event in breast carcinogenesis and is potentially reversible. This makes methylation a possible therapeutic target, a marker for treatment response and/or a prognostic factor. Methylation status of 40 tumor suppressor genes was...

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Autores principales: Schrijver, Willemijne A. M. E., Jiwa, Laura S., van Diest, Paul J., Moelans, Cathy B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408366/
https://www.ncbi.nlm.nih.gov/pubmed/25841351
http://dx.doi.org/10.1007/s10549-015-3362-y
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author Schrijver, Willemijne A. M. E.
Jiwa, Laura S.
van Diest, Paul J.
Moelans, Cathy B.
author_facet Schrijver, Willemijne A. M. E.
Jiwa, Laura S.
van Diest, Paul J.
Moelans, Cathy B.
author_sort Schrijver, Willemijne A. M. E.
collection PubMed
description Promoter hypermethylation of tumor suppressor genes seems to be an early event in breast carcinogenesis and is potentially reversible. This makes methylation a possible therapeutic target, a marker for treatment response and/or a prognostic factor. Methylation status of 40 tumor suppressor genes was compared between 53 primary breast tumors and their corresponding metastases to brain, lung, liver, or skin. In paired analyses, a significant decrease in methylation values was seen in distant metastases compared to their primaries in 21/40 individual tumor suppressor genes. Furthermore, primary tumors that metastasized to the liver clustered together, in line with the finding that primary breast carcinomas that metastasized to the brain, skin, or lung, showed higher methylation values in up to 27.5 % of tumor suppressor genes than primary carcinomas that metastasized to the liver. Conversion in methylation status of several genes from the primary tumor to the metastasis had prognostic value, and methylation status of some genes in the metastases predicted survival after onset of metastases. Methylation levels for most of the analyzed tumor suppressor genes were lower in distant metastases compared to their primaries, pointing to the dynamic aspect of methylation of these tumor suppressor genes during cancer progression. Also, specific distant metastatic sites seem to show differences in methylation patterns, implying that hypermethylation profiles of the primaries may steer site-specific metastatic spread. Lastly, methylation status of the metastases seems to have prognostic value. These promising findings warrant further validation in larger patient cohorts and more tumor suppressor genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-015-3362-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-44083662015-04-30 Promoter hypermethylation profiling of distant breast cancer metastases Schrijver, Willemijne A. M. E. Jiwa, Laura S. van Diest, Paul J. Moelans, Cathy B. Breast Cancer Res Treat Preclinical Study Promoter hypermethylation of tumor suppressor genes seems to be an early event in breast carcinogenesis and is potentially reversible. This makes methylation a possible therapeutic target, a marker for treatment response and/or a prognostic factor. Methylation status of 40 tumor suppressor genes was compared between 53 primary breast tumors and their corresponding metastases to brain, lung, liver, or skin. In paired analyses, a significant decrease in methylation values was seen in distant metastases compared to their primaries in 21/40 individual tumor suppressor genes. Furthermore, primary tumors that metastasized to the liver clustered together, in line with the finding that primary breast carcinomas that metastasized to the brain, skin, or lung, showed higher methylation values in up to 27.5 % of tumor suppressor genes than primary carcinomas that metastasized to the liver. Conversion in methylation status of several genes from the primary tumor to the metastasis had prognostic value, and methylation status of some genes in the metastases predicted survival after onset of metastases. Methylation levels for most of the analyzed tumor suppressor genes were lower in distant metastases compared to their primaries, pointing to the dynamic aspect of methylation of these tumor suppressor genes during cancer progression. Also, specific distant metastatic sites seem to show differences in methylation patterns, implying that hypermethylation profiles of the primaries may steer site-specific metastatic spread. Lastly, methylation status of the metastases seems to have prognostic value. These promising findings warrant further validation in larger patient cohorts and more tumor suppressor genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-015-3362-y) contains supplementary material, which is available to authorized users. Springer US 2015-04-05 2015 /pmc/articles/PMC4408366/ /pubmed/25841351 http://dx.doi.org/10.1007/s10549-015-3362-y Text en © The Author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial 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.
spellingShingle Preclinical Study
Schrijver, Willemijne A. M. E.
Jiwa, Laura S.
van Diest, Paul J.
Moelans, Cathy B.
Promoter hypermethylation profiling of distant breast cancer metastases
title Promoter hypermethylation profiling of distant breast cancer metastases
title_full Promoter hypermethylation profiling of distant breast cancer metastases
title_fullStr Promoter hypermethylation profiling of distant breast cancer metastases
title_full_unstemmed Promoter hypermethylation profiling of distant breast cancer metastases
title_short Promoter hypermethylation profiling of distant breast cancer metastases
title_sort promoter hypermethylation profiling of distant breast cancer metastases
topic Preclinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408366/
https://www.ncbi.nlm.nih.gov/pubmed/25841351
http://dx.doi.org/10.1007/s10549-015-3362-y
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