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The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma

Oncogene volume 29, pages 6138–6148 (2010)Cite this article

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Abstract

Genomic translocations have been implicated in cancer. In this study, we performed a screen for genetic translocations in gliomas based on exon-level expression profiles. We identified a translocation in the contactin-associated protein-like 2 (CASPR2) gene, encoding a cell adhesion molecule. CASPR2 mRNA was fused to an expressed sequence tag that likely is part of the nuclear receptor coactivator 1 gene. Despite high mRNA expression levels, no CASPR2 fusion protein was detected. In a set of 25 glioblastomas and 22 oligodendrogliomas, mutation analysis identified two additional samples with genetic alterations in the CASPR2 gene and all three identified genetic alterations are likely to reduce CASPR2 protein expression levels. Methylation of the CASPR2 gene was also observed in gliomas and glioma cell lines. CASPR2-overexpressing cells showed decreased proliferation rates, likely because of an increase in apoptosis. Moreover, high CASPR2 mRNA expression level is positively correlated with survival and is an independent prognostic factor. These results indicate that CASPR2 acts as a tumor suppressor gene in glioma.

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Authors and Affiliations

  1. Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands

    L B C Bralten, A M Gravendeel, N K Kloosterhof, M J van den Bent, P A E Sillevis Smitt & P J French

  2. Department of Pediatric Oncology and Hematology, Erasmus Medical Center, Rotterdam, The Netherlands

    N K Kloosterhof

  3. Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands

    A Sacchetti & J M Kros

  4. Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    T Vrijenhoek & J A Veltman

  5. Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands

    C C Hoogenraad

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Correspondence to P J French.

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Bralten, L., Gravendeel, A., Kloosterhof, N. et al. The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma. Oncogene 29, 6138–6148 (2010). https://doi.org/10.1038/onc.2010.342

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