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Open Access 01-05-2015 | Preclinical study

Promoter hypermethylation profiling of distant breast cancer metastases

Authors: Willemijne A. M. E. Schrijver, Laura S. Jiwa, Paul J. van Diest, Cathy B. Moelans

Published in: Breast Cancer Research and Treatment | Issue 1/2015

Abstract

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.

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Title: Promoter hypermethylation profiling of distant breast cancer metastases
Authors: Willemijne A. M. E. Schrijver
Laura S. Jiwa
Paul J. van Diest
Cathy B. Moelans
Publication date: 01-05-2015
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2015
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-015-3362-y

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