PMID- 18810378 OWN - NLM STAT- MEDLINE DCOM- 20090326 LR - 20181113 IS - 0946-2716 (Print) IS - 0946-2716 (Linking) VI - 86 IP - 12 DP - 2008 Dec TI - Chromosomal changes characterize head and neck cancer with poor prognosis. PG - 1353-65 LID - 10.1007/s00109-008-0397-0 [doi] AB - 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. FAU - Bauer, Verena L AU - Bauer VL AD - Institute of Molecular Radiation Biology, Helmholtz Center Munich German Research Center for Environmental Health GmbH, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany. FAU - Braselmann, Herbert AU - Braselmann H FAU - Henke, Michael AU - Henke M FAU - Mattern, Dominik AU - Mattern D FAU - Walch, Axel AU - Walch A FAU - Unger, Kristian AU - Unger K FAU - Baudis, Michael AU - Baudis M FAU - Lassmann, Silke AU - Lassmann S FAU - Huber, Reinhard AU - Huber R FAU - Wienberg, Johannes AU - Wienberg J FAU - Werner, Martin AU - Werner M FAU - Zitzelsberger, Horst F AU - Zitzelsberger HF LA - eng PT - Journal Article DEP - 20080923 PL - Germany TA - J Mol Med (Berl) JT - Journal of molecular medicine (Berlin, Germany) JID - 9504370 RN - 0 (Biomarkers, Tumor) SB - IM MH - Adult MH - Biomarkers, Tumor/*analysis MH - Carcinoma, Squamous Cell/diagnosis/*genetics/pathology MH - *Chromosome Aberrations MH - Comparative Genomic Hybridization MH - Female MH - Head and Neck Neoplasms/diagnosis/*genetics/pathology MH - Humans MH - Male MH - Prognosis EDAT- 2008/09/24 09:00 MHDA- 2009/03/27 09:00 CRDT- 2008/09/24 09:00 PHST- 2008/03/14 00:00 [received] PHST- 2008/07/23 00:00 [accepted] PHST- 2008/07/08 00:00 [revised] PHST- 2008/09/24 09:00 [pubmed] PHST- 2009/03/27 09:00 [medline] PHST- 2008/09/24 09:00 [entrez] AID - 10.1007/s00109-008-0397-0 [doi] PST - ppublish SO - J Mol Med (Berl). 2008 Dec;86(12):1353-65. doi: 10.1007/s00109-008-0397-0. Epub 2008 Sep 23.