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Methylation profiles of 22 candidate genes in breast cancer using high-throughput MALDI-TOF mass array

Abstract

Alterations of DNA methylation patterns have been suggested as biomarkers for diagnostics and therapy of cancers. Every novel discovery in the epigenetic landscape and every development of an improved approach for accurate analysis of the events may offer new opportunity for the management of patients. Using a novel high-throughput mass spectrometry on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) silico-chips, we determined semiquantitative methylation changes of 22 candidate genes in breast cancer tissues. For the first time we analysed the methylation status of a total of 42 528 CpG dinucleotides on 22 genes in 96 different paraffin-embedded tissues (48 breast cancerous tissues and 48 paired normal tissues). A two-way hierarchical cluster analysis was used to classify methylation profiles. In this study, 10 hypermethylated genes (APC, BIN1, BMP6, BRCA1, CST6, ESRb, GSTP1, P16, P21 and TIMP3) were identified to distinguish between cancerous and normal tissues according to the extent of methylation. Individual assessment of the methylation status for each CpG dinucleotide indicated that cytosine hypermethylation in the cancerous tissue samples was mostly located near the consensus sequences of the transcription factor binding sites. These hypermethylated genes may serve as biomarkers for clinical molecular diagnosis and targeted treatments of patients with breast cancer.

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Acknowledgements

We thank Professor Charles Cantor (SEQUENOM) for reading the manuscript and making critical comments, Vivian Kiefer for her excellent assistance and Regan Geissmann for proofreading the text. We are indebted to the patients for their cooperation. This work was supported in part by Swiss National Science Foundation (320000-119722/1) and Swiss Cancer League, Krebsliga Beider Basel and Dr Hans Altschueler Stiftung.

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Correspondence to X Y Zhong.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Radpour, R., Kohler, C., Haghighi, M. et al. Methylation profiles of 22 candidate genes in breast cancer using high-throughput MALDI-TOF mass array. Oncogene 28, 2969–2978 (2009). https://doi.org/10.1038/onc.2009.149

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