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Cyclin D1 Genotype and Expression in Sporadic Hemangioblastomas

  • Laboratory Investigation
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Summary

Central nervous system (CNS) hemangioblastomas are highly-vascularized tumors occurring in sporadic form or as a manifestation of von Hippel–Lindau disease (VHL). The VHL protein (pVHL) regulates various target genes, one of which is the CCND1 gene, encoding cyclin D1, a protein that plays a critical role in the control of the cell cycle. Overexpression of cyclin D1 is found in many cancers. The CCND1 gene contains a common G → A polymorphism (870G > A) that enhances alternative splicing of the gene. CCND1 genotype is associated with clinical outcome in a number of cancers although prognostic significance varies with tumor type. In VHL disease, CCND1 genotype has been suggested as a genetic modifier that influences susceptibility to hemangioblastomas.

In order to analyze whether CCND1 genotype plays a role in sporadic CNS hemangioblastomas, we investigated CCND1 genotype in tumor tissue of 17 sporadic and also in five VHL-related CNS hemangioblastomas. In addition, in these tumors the extent and localization of cyclin D1 expression was investigated by immunohistochemistry. We found no deviation in CCND1 genotype distribution and allele frequencies from expected values. Also, there was no correlation between age at onset and CCND1 genotype. The expression of cyclin D1 as detected by immunohistochemistry was highly variable within and between tumors, without a clear correlation with CCND1 genotype. We conclude that, whereas variable but sometimes high cyclin D1 expression is a feature of sporadic hemangioblastomas, CCND1 genotype is unlikely to be an important genetic modifier in the oncogenesis of these tumors.

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Authors and Affiliations

  1. Department of Neurology, Radboud University, Nymegen Medical Center, P.O. Box 9101, 6500, HB, Nijmegen, The Netherlands

    Johanna M. M. Gijtenbeek, Sandra H. E. Boots-Sprenger & Judith W. M. Jeuken

  2. Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

    Barbara Franke

  3. Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

    Pieter Wesseling & Judith W. M. Jeuken

Authors
  1. Johanna M. M. Gijtenbeek
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  2. Sandra H. E. Boots-Sprenger
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  3. Barbara Franke
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  4. Pieter Wesseling
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  5. Judith W. M. Jeuken
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Correspondence to Johanna M. M. Gijtenbeek.

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Gijtenbeek, J.M.M., Boots-Sprenger, S.H.E., Franke, B. et al. Cyclin D1 Genotype and Expression in Sporadic Hemangioblastomas. J Neurooncol 74, 261–266 (2005). https://doi.org/10.1007/s11060-004-7326-z

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