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Chromosomal changes characterize head and neck cancer with poor prognosis

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Abstract

It is well established that genetic alterations may be associated to prognosis in tumor patients. This study investigates chromosomal changes that predict the clinical outcome of head and neck squamous cell carcinoma (HNSCC) and correlate to characteristic clinicopathological parameters. We applied comparative genomic hybridization (CGH) to tissue samples from 117 HNSCC patients scheduled for radiotherapy. Genomic aberrations occurring in more than five patients were studied for impact on locoregional progression (LRP)-free survival. p values were adjusted by the Hochberg–Benjamini procedure and significant aberrations and clinical variables subjected to a stepwise backwards Cox proportional model. Significant alterations were further analyzed by array-CGH and fluorescence in situ hybridization (FISH). In multivariate survival analysis gains on 1q and 16q predict reduced LRP-free survival independently from known prognostic factors. Cluster analysis separated the HNSCC cases into two groups (cluster 1 and 2) that are characterized by significant differences for imbalances in 13 chromosomal regions. Moreover, it became apparent that cluster 1 correlates to nonanemic patients, while cluster 2 represents predominantly anemic cases. Array-CGH pinpoints 16q24.3 to be the region of interest on chromosome 16 which was further verified by FISH analysis where an increased copy number of FANCA, a member of the Fanconi anemia/breast cancer pathway, could be identified. This study demonstrates that chromosomal gains on 1q and 16q as well as chromosomal loss on 18q represent prognostic markers in HNSCC and that these alterations may explain to some extent the dismal course of a subgroup of patients.

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Acknowledgements

The skilful technical assistance of E. Konhäuser and Anja Schöpflin is gratefully acknowledged. We would like to acknowledge Cordelia Langford and the Wellcome Trust Sanger Institute microarray facility for providing the 1-Mb BAC arrays.

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Authors and Affiliations

  1. Institute of Molecular Radiation Biology, Helmholtz Center Munich German Research Center for Environmental Health GmbH, Ingolstaedter Landstraße 1, 85764, Neuherberg, Germany

    Verena L. Bauer, Herbert Braselmann, Kristian Unger, Reinhard Huber & Horst F. Zitzelsberger

  2. Clinic for Radiation Therapy, University Clinic Freiburg, Robert-Koch-Strasse 3, 79106, Freiburg, Germany

    Michael Henke

  3. Institute of Pathology, University Clinic Freiburg, Breisacherstrasse 115a, 79106, Freiburg, Germany

    Dominik Mattern, Silke Lassmann & Martin Werner

  4. Institute of Pathology, Helmholtz Center Munich German Research Center for Environmental Health GmbH, Ingolstaedter Landstrasse 1, 85764, Neuherberg, Germany

    Axel Walch

  5. Institute of Molecular Biology, University of Zurich, Winterthurerstr. 190, 8057, Zurich, Switzerland

    Michael Baudis

  6. Department Biology II, Anthropology and Human Genetics, Ludwig-Maximilians University, Grosshaderner Str. 2, 82152, Martinsried, Germany

    Johannes Wienberg

  7. Department of Histopathology, Imperial College London, Hammersmith Hospital, 142 J Block, Du Cane Road, W12 0NN, London, UK

    Kristian Unger

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  1. Verena L. Bauer
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  2. Herbert Braselmann
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  11. Martin Werner
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  12. Horst F. Zitzelsberger
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Correspondence to Horst F. Zitzelsberger.

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Bauer, V.L., Braselmann, H., Henke, M. et al. Chromosomal changes characterize head and neck cancer with poor prognosis. J Mol Med 86, 1353–1365 (2008). https://doi.org/10.1007/s00109-008-0397-0

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  • DOI: https://doi.org/10.1007/s00109-008-0397-0

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