title: Chromosomal changes characterize head and neck cancer with poor prognosis.
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.
authors.affiliation: Institute of Molecular Radiation Biology, Helmholtz Center Munich German Research Center for Environmental Health GmbH, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: Verena L
authors.initials: VL
authors.lastname: Bauer
authors.forename: Herbert
authors.initials: H
authors.lastname: Braselmann
authors.forename: Michael
authors.initials: M
authors.lastname: Henke
authors.forename: Dominik
authors.initials: D
authors.lastname: Mattern
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
authors.forename: Kristian
authors.initials: K
authors.lastname: Unger
authors.forename: Michael
authors.initials: M
authors.lastname: Baudis
authors.forename: Silke
authors.initials: S
authors.lastname: Lassmann
authors.forename: Reinhard
authors.initials: R
authors.lastname: Huber
authors.forename: Johannes
authors.initials: J
authors.lastname: Wienberg
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
authors.forename: Horst F
authors.initials: HF
authors.lastname: Zitzelsberger
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor