Oncogenes serve as specific and unique targets for drug intervention to treat cancer, as their activation (amplification and activating mutation) is essential for tumor development. Targeting of oncogenes has proven clinically useful in treating patients with HER2/neu gene amplification and BCR/Abl oncogene activation. Likewise, amplification of specific oncogenes could be linked with disease stage and response of chemotherapy, suggesting oncogene amplification as potential biomarker for outcome prediction. Given significant clinical impact, identification and characterization of new oncogenes promise to advance clinical management of cancer patients. Unfortunately, only a few such crucial oncogenes have been identified in oral cancer. We propose to identify new oncogenes by screening amplified chromosomal regions in oral squamous cell carcinoma, most common type of oral cancer, using a rational and comprehensive approach. Recent completion of human genome project together with advances in genome-wide DNA and transcriptome-wide RNA analyses provides unprecedented opportunity for comprehensive analysis of human cancer genome in fine detail. With these innovations as robust tools, we can now measure gene copy number changes in cancer quantitatively, plus map those changes directly onto a human genome. Candidate genes with both amplification and over-expression were then analyzed for potential somatic activating mutation, using a high throughput sequencing platform. We expect analysis of oral cancer genome and identification of new oncogenes not only to shed light on pathogenesis of oral cancer but also lay groundwork for new diagnostic tests and novel therapeutic intervention for this devastating disease.
