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Whole genome DNA methylation signature of HER2-positive breast cancer
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Örebro University, School of Medicine, Örebro University, Sweden.
Department of Medical Biosciences/Clinical Chemistry, Umeå University, Umeå, Sweden.
Department of Medical Biosciences/Clinical Chemistry, Umeå University, Umeå, Sweden.
2014 (English)In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 9, no 8, 1149-1162 p.Article in journal (Refereed) Published
Abstract [en]

In order to obtain a comprehensive DNA methylation signature of HER2-positive breast cancer (HER2+ breast cancer), we performed a genome-wide methylation analysis on 17 HER2+ breast cancer and compared with ten normal breast tissue samples using the Illumina Infinium HumanMethylation450 BeadChip (450K). In HER2+ breast cancer, we found altered DNA methylation in genes involved in multicellular development, differentiation and transcription. Within these genes, we observed an overrepresentation of homeobox family genes, including several genes that have not been previously reported in relation to cancer (DBX1, NKX2-6, SIX6). Other affected genes included several belonging to the PI3K and Wnt signaling pathways. Notably, HER2, AKT3, HK1, and PFKP, genes for which altered methylation has not been previously reported, were also identified in this analysis. In total, we report 69 candidate biomarker genes with maximum differential methylation in HER2+ breast cancer. External validation of gene expression in a selected group of these genes (n = 13) revealed lowered mean gene expression in HER2+ breast cancer. We analyzed DNA methylation in six top candidate genes (AKR1B1, INA, FOXC2, NEUROD1, CDKL2, IRF4) using EpiTect Methyl II Custom PCR Array and confirmed the 450K array findings. Future clinical studies focusing on these genes, as well as on homeobox-containing genes and HER2, AKT3, HK1, and PFKP, are warranted which could provide further insights into the biology of HER2+ breast cancer.

Place, publisher, year, edition, pages
Austin, USA: Landes Bioscience , 2014. Vol. 9, no 8, 1149-1162 p.
Keyword [en]
DNA methylation, HER2-positive breast cancer, Illumina Infinium HumanMethylation450 BeadChip
National Category
Medical and Health Sciences Cancer and Oncology
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-37169DOI: 10.4161/epi.29632ISI: 000341360600010PubMedID: 25089541Scopus ID: 2-s2.0-84905672549OAI: oai:DiVA.org:oru-37169DiVA: diva2:749865
Note

Funding Agencies:

Swedish Cancer Society

Örebro County Council

Lions Cancer Foundation, Uppsala

Nyckelfonden, Örebro

Available from: 2014-09-25 Created: 2014-09-25 Last updated: 2017-10-17Bibliographically approved

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Lindqvist, Breezy MalakkaranWingren, StenNilsson, Torbjorn K.
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School of Health and Medical Sciences, Örebro University, SwedenSchool of Medicine, Örebro University, Sweden
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Epigenetics
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