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  • Original Article
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Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma

Oncogene volume 25, pages 1733–1742 (2006)Cite this article

Abstract

Epigenetic alterations like DNA methylation and the resulting inactivation of cancer-related genes often contribute to the development of various cancers. To identify the genes that are silenced by aberrant methylation in renal cell carcinoma (RCC), we subjected two RCC lines to methylated CpG island amplification/representational difference analysis. This identified 27 CpG islands. Combined bisulfite restriction analysis of these CpG islands in primary RCC cases revealed that four were methylated in a tumor-specific manner. One of these was identified as the human homeo-box gene B13 (HOXB13) gene, but the remaining three CpG islands were not associated with known genes. The methylation frequencies of HOXB13 in primary RCC samples and lines were 30 and 73%, respectively. The methylation status of HOXB13 correlated with the loss of its expression both in RCC lines and primary tumors, and methyltransferase inhibitor treatment induced the recovery of its expression. Exogenous expression of HOXB13 in RCC cells that lacked endogenous HOXB13 expression suppressed colony formation and induced apoptotic features. Furthermore, HOXB13 methylation correlated positively with tumor grade and microvessel invasion. These results suggest that HOXB13 is a novel candidate tumor suppressor gene in RCC and that its inactivation may play an important role in both RCC tumorigenesis and progression.

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Acknowledgements

This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan.

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Authors and Affiliations

  1. Department of Urology, Kochi Medical School, Nankoku, Japan

    H Okuda, M Tsuchiya, M Kamada & T Shuin

  2. First Department of Internal Medicine, Sapporo Medical University, Sapporo, Japan

    M Toyota

  3. Department of Ophthalmology, Kochi Medical School, Nankoku, Japan

    W Ishida

  4. Department of Tumor Pathology, Kochi Medical School, Nankoku, Japan

    M Furihata

  5. Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University, Sapporo, Japan

    M Toyota & T Tokino

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  1. H Okuda
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  2. M Toyota
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Correspondence to H Okuda.

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Okuda, H., Toyota, M., Ishida, W. et al. Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma. Oncogene 25, 1733–1742 (2006). https://doi.org/10.1038/sj.onc.1209200

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