Abstract 3939: Integrated genomic analysis of head and neck tumors reveals focal high-level copy number gains in chr11q13 are associated with increased expression of known regional oncogenes

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Background: Head and neck squamous cell carcinoma (HNSCC) is a complex and heterogeneous disease for which the underlying genomic aberrations are unknown. Previous studies have suggested that chr11q13 is a region of interest in HNSCC. Independent studies suggest that genes from this region may be important – for example, CTTN, CCND1, MYEOV, and ANO1 – but to our knowledge no studies have focused on the integration of copy number data and potential targets, or investigated the prevalence of copy number aberrations (CNAs) and clinical covariates. Human papillomavirus-associated HNSCC (HPV-HNSCC) is of particular interest, and it is known that HPV-HNSCC is most commonly found in the oropharynx. However, to our knowledge no studies have examined the association between CNAs of chr11q13 and patient outcome for patients with oropharynx tumors. Techniques: After receiving informed consent, we obtained tumor samples from an incident surgical series of HNSCC patients at the University of North Carolina Hospital. Copy number (CN) and gene expression (GE) assays were performed using Affymetrix Genome-Wide SNP6.0 and Agilent 44K Gene Expression platfoms, respectively. CN values were subsequently analyzed for amplifications in region of chr11q13 using an amplification threshold equivalent to at least a 50% increase in copy number. Results: Samples from 162 patients were obtained, making this the largest genomic HNSCC series ever reported to our knowledge. After passing quality control on both platforms, CN, GE, and clinical data was available for 86 patients in the integrated analysis. Data from the remaining 76 samples was also reviewed, and for these samples either CN, GE, or clinical information is available. We estimate that amplifications of chr11q13 are found in approximately 30% of all HNSCC patients. The consensus region covers seven genes, and four of these genes – CTTN, CCND1, MYEOV, and ANO1 – have expression values that are statistically significantly correlated with copy number, supporting existing literature both for the region and these genes. If attention is restricted to patients with oropharynx tumors, we find that patients with chr11q13 amplifications have an increased risk of recurrence or death when compared to patients without chr11q13 amplifications. These amplifications are highly overlapping with smoking status in oropharynx patients, suggesting a potential mechanism for the worse outcome seen in HPV positive smokers relative to nonsmokers (N Eng J Med 2007;356:1944-1956). Conclusion: Integrated genomic analysis unmasks frequent copy number gains in chr11q13. Copy number values in chr11q13 are associated with expression of known regional oncogenes. We suggest a potential explanation for the worse clinical outcomes seen in HPV positive smokers. 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 3939. doi:10.1158/1538-7445.AM2011-3939