Abstract 111: Recurrent mutations of CDKN2A genes characterize worse prognosis of HPV positive and negative oropharyngeal squamous cell carcinoma

Background: Oropharyngeal squamous cell carcinoma (OSCC) exhibits unique clinical and molecular characteristics, depending on its association with high-risk human papillomavirus (HPV) or other carcinogen like smoking1. Considering significant subset of patients with OSCC still exhibits poor response to contemporary treatments2, which frequently cause significant toxicity, a more detailed understanding of these poor responders, especially adopting current precision genomic technology, could provide a clue for developing better treatment. Methods: In this study, we gathered the somatic point mutations and mRNA expression data of 520 OSCC patients from The Cancer Genome Atlas (TCGA) and then investigated recurrent somatic point mutations. To genes having the recurrent and same type point mutations, in addition, we check out the mRNA expression and analyzed a survival analysis. Results: We found 7 somatic point mutations of CDKN2A gene, which having recurrent patients and only nonsense SNVs. Out of these mutation, 6 recurrent point mutations of CDKN2A gene have highly expressed on PIK3CA, FGFR2 and FGFR3 genes, as well as showed a significant deterioration on survival outcome. Conclusion: Recurrent nonsense mutations of CDKN2A mostly (6/7, 85.7%) derived an abnormal regulation of other genes, such as PI3KA, FGFR2, and FGFR3. Moreover, this pattern of mutations significantly characterizes ominous prognosis in HPV positive and negative OSCC. Our result might provide better insights for characterizing the subgroup of OSCC and eventual development of precision strategy for this disease subset. References 1. Licitra, L. et al. High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma. J Clin Oncol 24, 5630-6 (2006). 2. Ang, K.K. et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363, 24-35 (2010). Citation Format: Jongkeun Lee, Dongwan Hong, Eun Kyung Lee, Yuh-Seog Jung, Weon Seo Park. Recurrent mutations of CDKN2A genes characterize worse prognosis of HPV positive and negative oropharyngeal squamous cell carcinoma. [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 111.