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Common mutations of β-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region

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Abstract

Dysregulation of the Wnt signalling pathway contributes to developmental abnormalities and carcinogenesis of solid tumours. Here, we examined β-catenin and adenomatous polyposis coli (APC) by mutational analysis in pituitary adenomas (n=60) and a large series of craniopharyngiomas (n=41). Furthermore, the expression pattern of β-catenin was immunohistochemically analysed in a cohort of tumours and cysts of the sellar region including pituitary adenomas (n=58), craniopharyngiomas (n=57), arachnoidal cysts (n=8), Rathke’s cleft cysts (n=10) and xanthogranulomas (n=6). Whereas APC mutations were not detectable in any tumour entity, β-catenin mutations were present in 77% of craniopharyngiomas, exclusively of the adamantinomatous subtype. All mutations affected exon 3, which encodes the degradation targeting box of β-catenin compatible with an accumulation of nuclear β-catenin protein. In addition, a novel 81-bp deletion of this exonic region was detected in one case. Immunohistochemical analysis confirmed a shift from membrane-bound to nuclear accumulation of β-catenin in 94% of the adamantinomatous tumours. Aberrant distribution patterns of β-catenin were never observed in the other tumour entities under study. We conclude that β-catenin mutations and/or nuclear accumulation serve as diagnostic hallmarks of the adamantinomatous variant, setting it apart from the papillary variant of craniopharyngioma.

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Acknowledgments

We thank Dr. I. Blümcke (University of Erlangen, Germany) and Dr. A. Koch (University of Bonn, Germany) for helpful discussions. We thank V. Schmidt, S. Gutmann and B. Rings for expert technical assistance. The work is supported by ELAN and Marohn funds from the University of Erlangen Medical Faculty.

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Authors and Affiliations

  1. Department of Neuropathology, Friedrich-Alexander University Erlangen-Nuremberg, Krankenhausstrasse 8–10, 91054, Erlangen, Germany

    Rolf Buslei, Michael Nolde, Stephan Meissner, Florian Siebzehnrübl & Eric Hahnen

  2. Department of Neurosurgery, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

    Bernd Hofmann, Ilker Y. Eyupoglu, Jürgen Kreutzer & Rudolf Fahlbusch

  3. Department of Human Genetics, University Cologne, Köln, Germany

    Eric Hahnen

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  1. Rolf Buslei
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Correspondence to Rolf Buslei.

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Buslei, R., Nolde, M., Hofmann, B. et al. Common mutations of β-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region. Acta Neuropathol 109, 589–597 (2005). https://doi.org/10.1007/s00401-005-1004-x

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  • DOI: https://doi.org/10.1007/s00401-005-1004-x

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