Abstract 5083: Analysis of head and neck cancer reveals recurrent copy number aberrations and molecular subtypes exhibiting distinct expression patterns of known oncogenes in the chr3q amplicon
Authors: Walter Vonn , Wilkerson Matthew , Cabanski Chris , Du Ying , Hayward Michele , Hill Ashley , Zhao Ni , Yin Xiaoying , Hayes Neil 
Published: August 2012

Background: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease whose underlying etiology is unknown. Chung et al. (Cancer Cell 2004; 5: 489 - 500) detected HNSCC gene expression (GE) subtypes, but to our knowledge these subtypes have not been discovered in other HNSCC datasets. Moreover, we are not aware of any HNSCC studies that have examined recurrent DNA copy number (CN) aberrations in the context of GE subtypes. Numerous studies have shown that HNSCC exhibits recurrent copy number gains in chr3q26-28, a region that contains the known oncogenes SOX2, PIK3CA, and TP63. Bass et al. (Nature Genetics 2009; 41(11): 1238 - 1242) suggest that SOX2 plays a fundamental role in the development of esophageal SCC. However, it does not appear that the expression patterns of SOX2, PIK3CA, and TP63 have been investigated in HNSCC. Techniques: After receiving informed consent, we obtained tumor samples from an incident surgical series of HNSCC patients at the University of North Carolina Hospital. CN and GE assays were performed using Affymetrix Genome-Wide SNP6.0 and Agilent 44K Gene Expression platforms, respectively. GE subtypes were discovered using ConsensusClusterPlus, and their statistical significance was assessed with SigClust. DiNAMIC was used to detect recurrent CN aberrations. Results: Tumor samples from 169 patients were obtained, making this the largest genomic HNSCC series ever reported to our knowledge. After passing quality control on both platforms, GE data was available for 138 patients, while CN data was available for 110 patients; GE and CN data was available for 82 patients. Four GE subtypes were found, and all pairwise comparisons of these subtypes were statistically significant after adjusting for multiple testing. Nearest centroid methods show that our GE subtypes correspond to those of Chung et al.; three of our four GE subtypes show strong similarities to those found in lung squamous cell carcinoma. Overall, recurrent CN gains were discovered in chr3q27, chr11q13, and chr8q23; recurrent CN losses were found in chr3p21, chr9p21, and chr8p23. All of these regions harbor known oncogenes. Distinct patterns of recurrent gains and losses were noted when CN data from each GE subtype was examined, and different patterns of gain and loss were found when we examined CN data from each tumor site. Although the expression subtypes exhibit similar CN values in the chr3q26-28 amplicon, the expression patterns of SOX2, PIK3CA, and TP63 differ considerably. Conclusion: Integrated genomic analysis reveals HNSCC GE subtypes, some of which are present in lung cancer. The existence of distinct patterns of CN gain and loss in the GE subtypes suggests the presence of multiple biological pathways that play fundamental roles in the development of HNSCC.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5083. doi:1538-7445.AM2012-5083