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High-throughput assessment of CpG site methylation for distinguishing between HCV-cirrhosis and HCV-associated hepatocellular carcinoma

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Abstract

Methylation of promoter CpG islands has been associated with gene silencing and demonstrated to lead to chromosomal instability. Therefore, some postulate that aberrantly methylated CpG regions may be important biomarkers indicative of cancer development. In this study we used the Illumina GoldenGate Methylation BeadArray Cancer Panel I for simultaneously profiling methylation of 1,505 CpG sites in order to identify methylation differences in 76 liver tissues ranging from normal to pre-neoplastic and neoplastic states. CpG sites for ESR1, GSTM2, and MME were significantly differentially methylated when comparing the pre-neoplastic tissues from patients with concomitant hepatocellular carcinoma (HCC) to the pre-neoplastic tissues from patients without HCC. When comparing paired HCC tissues to their corresponding pre-neoplastic non-tumorous tissues, eight CpG sites, including one CpG site that was hypermethylated (APC) and seven (NOTCH4, EMR3, HDAC9, DCL1, HLA-DOA, HLA-DPA1, and ERN1) that were hypomethylated in HCC, were identified. Our study demonstrates that high-throughput methylation technologies may be used to identify differentially methylated CpG sites that may prove to be important molecular events involved in carcinogenesis.

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Acknowledgments

This project was supported by a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant, RO1DK069859.

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Authors and Affiliations

  1. Department of Biostatistics, Virginia Commonwealth University, 730 East Broad Street, P.O. Box 980032, Richmond, VA, 23298-0032, USA

    Kellie J. Archer

  2. Department of Surgery, Division of Transplantation, Virginia Commonwealth University, Richmond, VA, 23298, USA

    Kellie J. Archer, Valeria R. Mas, Daniel G. Maluf & Robert A. Fisher

  3. Department of Pathology, Virginia Commonwealth University, Richmond, VA, 23298, USA

    Valeria R. Mas

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  1. Kellie J. Archer
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  2. Valeria R. Mas
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Correspondence to Kellie J. Archer.

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Communicated by S. Hohmann.

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Archer, K.J., Mas, V.R., Maluf, D.G. et al. High-throughput assessment of CpG site methylation for distinguishing between HCV-cirrhosis and HCV-associated hepatocellular carcinoma. Mol Genet Genomics 283, 341–349 (2010). https://doi.org/10.1007/s00438-010-0522-y

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  • DOI: https://doi.org/10.1007/s00438-010-0522-y

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