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.

Down‐regulation of miRNA‐204 by LMP‐1 enhances CDC42 activity and facilitates invasion of EBV‐associated nasopharyngeal carcinoma cells

“…In addition, miR-204 is located at the cancer-associated genomic region 9q21.1-q22.3 locus in human head and neck cancer [16][17][18].…”

Pyrosequencing-based DNA methylation profiling of Fanconi anemia/BRCA pathway genes in laryngeal squamous cell carcinoma

“…FANCA has been previously screened in various cancers for genetic and epigenetic alterations. Moreover, in the array-based analysis of Bauer et al (39) the region 16q23-q24 harboring the FANCA gene showed a significant gain associated with lower survival rates in HNSCC patients. Hypomethylation described in this study may be an alternative mechanism to gene amplification potentially leading to an increased gene activity.…”

DNA Repair Capacity and the Risk of Head and Neck Cancer

“…Clustering both DNA strands significantly reduces ability of DNA repair machinery to operate, and repair of cross-link involve a highly complexed networks. At the higher structural rank this cause high chromosomal instability (Bauer et al, 2008).…”

“…Some array-based data (Sparano et al, 2006) demonstrates the copy number alterations (CNA) in regions covering FA genes BRCA1, BRCA2, FANCD2, and FANCG but no direct associations with the disease were found. In contrast, FANCA has been analyzed in arrayCGH-based study (Bauer et al, 2008), where the region 16q23-q24 (FANCA locus) showed a significant gain associated with lower survival rates in HNSCC patients.…”