Abstract To uncover genomic alterations that can be used as molecular markers for oral cavity squamous cell carcinoma (OSCC) in Taiwan, we recruited patients who were ethnically Taiwanese and admitted to Chang Gung Memorial Hospital at Taipei. We performed whole-exome sequencing (WES) of matched tumor/PBMC DNAs from 50 OSCC patients (75-Mbp target region, mean depth = 244 ± 54), and RNA sequencing of matched tumor/adjacent normal tissues from 39 of the 50 patients (mean read count = 38.7 ± 15.2 million). A subset of the identified somatic mutations was validated in 49 tumor tissues using an IonAmpliSeqTM Comprehensive Cancer Panel (CCP; 409 cancer-related genes). In total, our exome sequencing analyses uncovered 33,160 somatic single nucleotide variants (SNVs) and InDels. The targeted approach of CCP enabled us to independently validate 84.91% of the SNVs identified by our whole-exome sequencing. We cross-referenced our data with that of 172 oral cavity cancer samples (OSCC-TCGA) from the Head-Neck Squamous Cell Carcinoma (HNSC) project of TCGA (HNSC-TCGA) and 106 from India (OSCC-India), as annotated in the International Cancer Genome Consortium (ICGC). We found that our patient cohort was characteristic of OSCC with regard to frequently mutated genes, such as CDKN2A, TP53, and NOTCH1. Interestingly, however, our analysis further identified mutations in seven other genes that turned out to be unique, locally prevalent (>10% of patients) alterations. We further used our exome sequencing data to examine copy number alterations in our samples and our findings largely recapitulated the profile found in OSCC-TCGA, which included significantly amplified/deleted regions encompassing genes such as EGFR, FGFR1, FADD, FAT1 and CDKN2A. Comparative analysis of the transcriptomes of tumor and normal tissues allowed us to identify 3,548 genes as being differentially expressed in OSCC-Taiwan; these included 1,220 up-regulated and 2,328 down-regulated genes. Notably, 91.3% of these differentially expressed genes were similarly identified in the OSCC-TCGA data, indicating that the overall expression profile of OSCC is highly similar across ethnic groups. In the meeting, I will report the unique genomic alterations with the potential biomarkers in OSCC, and these findings might introduce a hitherto unknown genetic component of this disease. Citation Format: Kai-Ping Chang, Ting-Wen Chen, Curtis R. Pickering, Jeffrey N. Myers, Yu-Sun Chang. Integrated omics analyses identify prognostic biomarkers of oral cavity squamous cell carcinoma in Taiwan [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr IA10.