Abstract 809: High-resolution genomic profiling reveals gains of CCND1 and EGFR associated with disease progression in Taiwanese oral cavity squamous cell carcinomas.

Abstract

Abstract The genetic mechanisms underlying Taiwanese oral cavity squamous cell carcinoma (OSCC) are still largely unknown. We used high-resolution single nucleotide polymorphism microarrays (Affymetrix 500K) to detect copy number alterations (CNAs) in 26 OSCC tumor tissues. 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. Genomic Identification of Significant Targets in Cancer (GISTIC) analysis (version 2.0) was used to identify significant CNAs using a residual Q-value cutoff of 0.25. A total of 25 significant regions (2 focal amplifications and 23 deletions) were identified. The well known oncogene EGFR and CCND1 are resided in these two focal amplification regions (7p11.2 and 11q13.3), respectively. Several candidate cancer related genes such as FHIT (3p14.2), FAT (4q35.1), SH3GL2 (9p22.2) and ARHGAP21 (10p12.1) are known to locate in the identified 23 deletion regions. Furthermore, we found that 7p11.2 amplification and 4q35.2 deletion was mutually exclusive by ‘inter-target relationships’ (ITR) analysis using dimension reduction permutation (DRP) methods. Copy number gains of EGFR and CCND1 were also confirmed along with fluorescence in situ hybridization (FISH) and TaqMan CN assay (Hs01818912_cn and Hs00655630_cn), respectively. We found that the concordance rate was 70.59% for EGFR and 75.00% for CCND1. To further explore the clinical value of copy number gains of EGFR and CCND1 in OSCC, 182 OSCC cases were analyzed. Preliminary results indicated that gains of CCND1 were associated with tumor differentiation, lymph node metastasis and lymph node extracapsular spread (LNECS); while amplification of EGFR gene was significantly associated with tumor stage and lymph node metastasis but not LNECS. Furthermore, gains of CCND1 were significantly associated with poor disease-free and overall survival. On the other hand, amplification of EGFR was not associated with either disease-free or overall survival. Taken together, we have identified that gains of CCND1 and EGFR gene were significantly associated with disease progression in Taiwanese oral cavity squamous cell carcinomas. Citation Format: Huei-Tzu Chien, Shiang-Fu Huang, I-How Chen, Chun-Ta Liao, Hung-Ming Wang, Sou-De Cheng, Ling-Ling Hsieh. High-resolution genomic profiling reveals gains of CCND1 and EGFR associated with disease progression in Taiwanese oral cavity squamous cell carcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 809. doi:10.1158/1538-7445.AM2013-809