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  • Oncogenomics
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Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene

Oncogene volume 26, pages 3440–3449 (2007)Cite this article

Abstract

Inactivation of the HRPT2 gene encoding parafibromin was recently linked to the familial hyperparathyroidism-jaw tumor syndrome. Patients with this syndrome carry an increased risk of parathyroid and renal tumors. To determine the relevance of HRPT2 for sporadic renal tumors, clear cell, papillary and chromophobe renal cell carcinomas as well as oncocytomas and Wilms tumors were analysed for HRPT2 gene alterations. Loss of heterozygosity (LOH) of HRPT2 was found in seven of 56 (12.5%) clear cell, three of 14 (21%) papillary, six of 10 (60%) chromophobe renal cell carcinomas, three of eight (38%) oncocytomas and four of 10 (40%) Wilms tumors. In addition, two novel HRPT2 point mutations, causing K34Q and R292K changes in parafibromin, were detected in one clear cell carcinoma and one Wilms tumor, respectively. These tumors displayed LOH of the remaining wild-type allele, but interestingly no von Hippel–Lindau (VHL) mutation. Functional analysis revealed that the K34Q mutant species of parafibromin is, unlike wild-type protein, defective in suppressing cyclin D1 expression in vivo. Taken together, these results suggest that renal cancer-associated mutations in parafibromin occur in the absence of VHL mutation, which in turn may contribute to constitutively elevated cyclin D1 expression and abnormal cell proliferation.

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Acknowledgements

We thank Sonja Schmidt, Silvia Behnke and Martina Storz for technical assistance and staffs of our Molecular Diagnostic Laboratory for sequencing. We are also grateful to Nobert Wey for help with photographic and computer-assisted reproduction and to Dr Adriana von Teichman for English correction. AY is the recipient of a long-term Marie Curie intra-European fellowship. The study was supported by UBS AG (made possible by an anonymous donor), the Swiss National Science Foundation and the Zurich Cancer League, Switzerland.

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  1. Department of Pathology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland

    J Zhao, S Frigerio, A Perren, P Schraml, C Weisstanner, T Stallmach & H Moch

  2. Institute of Cell Biology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

    A Yart & W Krek

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  1. J Zhao
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Correspondence to J Zhao.

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Zhao, J., Yart, A., Frigerio, S. et al. Sporadic human renal tumors display frequent allelic imbalances and novel mutations of the HRPT2 gene. Oncogene 26, 3440–3449 (2007). https://doi.org/10.1038/sj.onc.1210131

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