Abstract 3911: Functional copy number alterations (CNAS) in oral cancer

Abstract

Abstract Background: Alterations in DNA copy number can functionally affect genes and produce a transformed cancer phenotype. Discoevery of novel cancer genes can be facilitated by identifying genomic regions undergoing frequent, significant alteration. Array comparative genomic hybridization techniques have generated vast amounts of raw copy number data requiring computational analysis to identify aberrations likely to be functional. In this analysis, we present data from a comprehensive computational approach designed to robustly map chromosomal aberrations in oral cavity squamous cell carcinoma (OCSCC). Methods: DNA was extracted from 31 microdissected OCSCC frozen tumors and hybridized with reference DNA on the Agilent 1M copy number array, containing nearly 1 million probes across the genome at high resolution. The RAE computational framework was used to identify CNAs. In this analysis, segmentation of probe data is first performed using paired reference HapMap data and individual-tumor thresholds to account for stromal admixture and tumor heterogeneity. Scores (single-copy gain, amplification, hemizygous loss, homozygous deletion) are then assigned, followed by soft discrimination thresholding and significance testing with false discovery rate correction. Regions of interest (ROIs) are then agnostically identified as regions of significant (FDR<0.01) alteration, expanded to adjacent loci to account for spatial and amplitude uncertainty. Finally, described copy number polymorphisms were excluded. Results: 49 ROIs were identified, 27 amplification regions (chromosomes 3,4,5,7,8,9,11,16,18,20,21) and 22 deletion regions (chromosomes 2,3,4,5,7,8,9,10,13,15,16,18,19). ROIs ranged in prevalence from 6.5-77.4% of samples, and encompassed 0-483 genes (total=2799, median=4), and 0-13 microRNAs (total=77, median=0). Eleven ROIs were focal intragenic CNAs. Four ROIs contained no named genes or microRNAs. Hierarchical clustering identified 3 clusters, based on escalating levels of CNA. Complete gene details of the 49 ROIs will be presented. Conclusions: We report significant regions of CNA in oral cancer, by applying a robust computational framework to identify recurrent chromosomal aberrations in OCSCC, which represent highly significant candidate functional events. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3911. doi:10.1158/1538-7445.AM2011-3911