Abstract 132: Comprehensive genomic analysis of human papillomavirus-associated oral cancers

Human papillomavirus-associated oral cancers comprise a distinct disease that is increasing in frequency in Western countries. Recent genomic landscape studies of oral cancers and of HPV-associated cervical cancers identified the most commonly mutated genes in each. Here we report a comprehensive analysis of 83 HPV-positive oropharyngeal cancers studied by whole genome sequencing (WGS), and an additional 46 tumors evaluated by the Cancer Genome Atlas project (TCGA) by exome sequencing. We confirmed recurrent mutations in previously reported, frequently mutated candidate driver genes including PIK3CA, as well as several novel gene targets, each occurring recurrently at frequencies of more than approximately 3%. Our WGS data demonstrated recurrent focal genomic instability associated with HPV insertional mutagenesis. We observed dramatic changes in genomic copy number variants (CNVs) at chromosome 3q as well as numerous other chromosomal regions that are recurrently gained or lost in HPV-positive tumors. RNA-Seq data from this collection of oral cancers defined differentially expressed transcript levels and other molecular alterations associated with single nucleotide variants (SNVs), CNVs and other genomic structural variants in the tumors. Together, our results reveal a unique pattern of somatic variants that distinguishes HPV+ oral cancers both from HPV- oral cancers as well as other HPV+ tumors arising in distinct tissues including the uterine cervix. These data shed new light on the molecular pathogenesis of oral cancers, and provide new opportunities for development of diagnostic and therapeutic strategies for affected patients. Citation Format: David E. Symer, Keiko Akagi, Kevin R. Coombes, Weihong Xiao, Robert K. L. Pickard, Amit Agrawal, Maura L. Gillison. Comprehensive genomic analysis of human papillomavirus-associated oral cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 132.