Abstract 5098: Identification of copy number alterations associated with the progression and clinical outcomes of oral cavity squamous cell carcinoma

Abstract

Abstract The molecular mechanisms contributing to the progression of oral cavity squamous cell carcinoma (OSCC) remain poorly understood. The primary treatment for advanced-stage OSCC is radical surgery with post-operative chemoradiation. However, the prognoses are usually discouraging. If we can better understand the characteristics of OSCCs, this may ultimately help clinicians to provide OSCC patients with more appropriate treatment. The advent of genome-wide profiling methods has opened up new possibility to catalogue chromosomal abnormal regions at high resolution. In the present study, 72 advanced-stage OSCCs were analyzed using two microarray platforms (26 cases with Affymetrix SNP 500K and 46 cases with Affymetrix SNP 6.0). Genomic copy number was determined by calculating the intensity ratio between the OSCC and a set of 270 normal DNAs from HapMap project. Segmented copy numbers for each tumor were inferred with the hidden markov model (HMM) using the Partek GS software. To identify regions for copy-number alterations (CNAs), GISTIC (genomic identification of significant targets in cancer) was applied to determine the significance. With this approach, 46 (14 gain and 32 loss) and 208 (48 gain and 160 loss) significant regions (FDR q-value < 0.25) were identified from SNP 500K and SNP 6.0 platform, respectively. Among them, 15 focal CNAs (8 gains (3q26.1, 7p11.2, 11q13.3, 13q22.1, 15q11.2, 17p13.3, 18p11.23-18p11.31, and 20p11.22) and 7 losses (1q21.1, 6p21.33, 7q31.3, 12q14.1, 2 focal regions in 14q11.2, 15q11.2)) are identical in these 2 platforms. Amplification of 11q13.3 containing a known oncogene CCND1 was confirmed by fluorescence in situ hybridization (FISH) with Vysis CCND1/CEP11 FISH probe kit. The clinicopathologic significances of these 15 CNAs were examined. Gain of 3q26.1 and 18p11.23-18p11.31, and loss of 15q11.2 were correlated significantly with lymph node metastasis. Furthermore, loss of two focal regions in 14q11.2 was significantly associated with disease-free and overall survival. In conclusion, CNAs associated with the progression and clinical outcomes of Taiwanese OSCC were identified by genomic approach using high-density SNP array. These results provide useful clues for future characterization of important oncogenes or tumor suppressor genes associated with the behaviors of the disease. 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 5098. doi:1538-7445.AM2012-5098