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Gene expression meta-analysis identifies chromosomal regions and candidate genes involved in breast cancer metastasis

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Breast Cancer Research and Treatment Aims and scope Submit manuscript

An Erratum to this article was published on 09 May 2008

Abstract

Breast cancer cells exhibit complex karyotypic alterations causing deregulation of numerous genes. Some of these genes are probably causal for cancer formation and local growth whereas others are causal for the various steps of metastasis. In a fraction of tumors deregulation of the same genes might be caused by epigenetic modulations, point mutations or the influence of other genes. We have investigated the relation of gene expression and chromosomal position, using eight datasets including more than 1200 breast tumors, to identify chromosomal regions and candidate genes possibly causal for breast cancer metastasis. By use of “Gene Set Enrichment Analysis” we have ranked chromosomal regions according to their relation to metastasis. Overrepresentation analysis identified regions with increased expression for chromosome 1q41–42, 8q24, 12q14, 16q22, 16q24, 17q12–21.2, 17q21–23, 17q25, 20q11, and 20q13 among metastasizing tumors and reduced gene expression at 1p31–21, 8p22–21, and 14q24. By analysis of genes with extremely imbalanced expression in these regions we identified DIRAS3 at 1p31, PSD3, LPL, EPHX2 at 8p21–22, and FOS at 14q24 as candidate metastasis suppressor genes. Potential metastasis promoting genes includes RECQL4 at 8q24, PRMT7 at 16q22, GINS2 at 16q24, and AURKA at 20q13.

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Acknowledgments

All the researchers that have generated gene expression data that we have included in the analysis are acknowledged for allowing us to use their data.

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Authors and Affiliations

  1. Department of Biochemistry, Pharmacology, and Genetics, Odense University Hospital and Human Microarray Centre (HUMAC), University of Southern Denmark, Odense, Denmark

    Mads Thomassen, Qihua Tan & Torben A. Kruse

  2. Institute of Public Health, University of Southern Denmark, Odense, Denmark

    Qihua Tan

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  1. Mads Thomassen
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  2. Qihua Tan
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Corresponding author

Correspondence to Mads Thomassen.

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Authors’ contributions

M. Thommassen and T. A. Kruse designed the study, Q. Tan developed methods for statistical analysis and M. Thommassen performed data analysis.

An erratum to this article can be found at http://dx.doi.org/10.1007/s10549-008-0038-x

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Thomassen, M., Tan, Q. & Kruse, T.A. Gene expression meta-analysis identifies chromosomal regions and candidate genes involved in breast cancer metastasis. Breast Cancer Res Treat 113, 239–249 (2009). https://doi.org/10.1007/s10549-008-9927-2

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  • DOI: https://doi.org/10.1007/s10549-008-9927-2

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