Abstract 3412: Distinct copy number alterations in genomes of oral cavity squamous cell carcinomas

Abstract

Abstract Oral cavity squamous cell carcinoma (OSCC) is one of the most common cancers in Taiwan and worldwide. Despite recent progress in the diagnosis and therapeutic modalities for OSCC, the 5-year survival rate has not been improved in recent two decades. In order to provide some clues for clinical management of OSCC, 72 advanced-stage OSCCs were analyzed using two microarray platforms (26 cases with Affymetrix 500K and 46 cases with Affymetrix SNP 6.0). Genomic copy number was derived from calculating the intensity ratio between the OSCC and a set of normal DNAs from HapMap project. Segmented copy numbers for each tumor were inferred with the hidden markov model using the Partek GS software and circular binary segmentation using GenePattern pipeline. Genomic Identification of Significant Targets in Cancer (GISTIC) analysis was used to identify significant copy number alterations (CNAs) using a Q-value cutoff of 0.25. With this approach, 41 (2 gain and 39 loss) and 32 (4 gain and 28 loss) significant regions were distinguished from 500K and SNP 6.0 platform, respectively. Among them, 12 (2 gains (7p11.2 and 11q13.3) and 10 losses (2q23.3-q24.2, 3p14.2-p12.1, 4q35.2, 7q33-q34, 9p21.3, 11q22.3-q24.3, 16q23.1, 18q11.2-q22.3, 21q21.1 and 21q22.3)) CNAs were identical in these two platforms. Two gain regions contained the well known oncogene EGFR (7p11.2) and CCND1 (11q13.3) and 10 deletion regions resides several known cancer suppressor genes such as FHIT (3p14.2-p12.1), FAT1 (4q35.1), CDKN2A (9p21.3) and ATM (11q22.3-q24.3). Among them, gain of 11q13.3 was correlated significantly with lymph node metastasis and loss of 4q35.2 was significantly associated with lymph node extracapsular spread (LNECS) and poor disease-free survival. Copy number gains of EGFR and CCND1 were further confirmed by fluorescence in situ hybridization and TaqMan CN assay (Hs01818912_cn and Hs02353610_cn), respectively. We found that the concordance rate was 74.63% for EGFR and 77.78% for CCND1. To further explore the clinical value of copy number gains of EGFR and CCND1 in OSCC, 257 OSCC cases were analyzed. Preliminary results indicated that gains of CCND1 were significantly associated with tumor differentiation, lymph node metastasis and 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 revealed the significant CNAs of OSCCs in Taiwan and confirmed the amplification of two important genes (CCND1 and EGFR) in 257 OSCCs. Thus, current genome-wide CNAs analysis provides clues for future characterization of important oncogenes and tumor suppressor genes associated with the behaviors of the disease. Citation Format: Huei-Tzu Chien, Shiang-Fu Huang, I-How Chen, Chun-Ta Liao, Hung-Ming Wang, Sou-De Cheng, Ling-Ling Hsieh. Distinct copy number alterations in genomes of oral cavity squamous cell carcinomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3412. doi:10.1158/1538-7445.AM2014-3412