Abstract
Oral squamous cell carcinoma (OSCC) is a common cancer in Taiwan and worldwide. To provide some clues for clinical management of OSCC, 72 advanced-stage OSCCs were analyzed using two microarray platforms (26 cases with Affymetrix 500 K and 46 cases with Affymetrix SNP 6.0). Genomic identification of significant targets in cancer analyses were used to identify significant copy number alterations (CNAs) using a q-value cutoff of 0.25. Among the several significant regions, 12 CNAs were common between these two platforms. Two gain regions contained the well-known oncogenes EGFR (7p11.2) and CCND1 (11q13.3) and several known cancer suppressor genes, such as FHIT (3p14.2–p12.1), FAT1 (4q35.1), CDKN2A (9p21.3), and ATM (11q22.3–q24.3), reside within the 10 deletion regions. Copy number gains of EGFR and CCND1 were further confirmed by fluorescence in situ hybridization and TaqMan CN assay, respectively, in 257 OSCC cases. Our results indicate that EGFR and CCND1 CNAs are significantly associated with clinical stage, tumor differentiation, and lymph node metastasis. Furthermore, EGFR and CCND1 CNAs have an additive effect on OSCC tumor progression. Thus, current genome-wide CNA analysis provides clues for future characterization of important oncogenes and tumor suppressor genes associated with the behaviors of the disease.
Highlights
Cancer is complicated in its behavior which is usually related with genomic instability [1].The genetic alterations are not the same in every tumor cell
It is worth noting that similar patterns of copy number (CN) gains and diverse patterns of CN losses were observed from these two platforms (Figure S2)
Based on the position of distinct copy number alterations (CNAs) estimated from genomic identification of significant targets in cancer (GISTIC), a total of 12 common distinct CNAs were identified by these two platforms (Table 2)
Summary
Cancer is complicated in its behavior which is usually related with genomic instability [1].The genetic alterations are not the same in every tumor cell. Cancer is complicated in its behavior which is usually related with genomic instability [1]. Oral cancer ranked fourth in the incidence of all cancers in Taiwan and is the sixth most common malignancy worldwide [3]. Areca quid (AQ), and alcohol are the three main environmental carcinogens for oral squamous cell carcinoma (OSCC) in Taiwan [4,5]. Several studies demonstrated that both tobacco and areca nut extract are toxic to cells and induce genome instability [6,7]. New radiation therapy techniques, target therapies and immuno-oncologic agents have been developed in cancer treatment but the advancements in the control of oral cancer were limited. The 5-year survival rate of OSCC has remained
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