Abstract 3874: Mutational landscapes of oral tongue squamous cell carcinoma reveal recurrent mutations in genes of therapeutic and prognostic relevance

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Carcinoma of the oral tongue (OTSCC) is the most common malignancy of the oral cavity, characterized by frequent recurrence and poor survival. The last three decades has witnessed a change in the OTSCC epidemiological profile, with increasing incidence in younger patients, females and never-smokers. This study aims to characterize the OTSCC genomic landscape and to determine factors that may delineate the genetic basis of this disease, inform prognosis and identify targets for therapeutic intervention. Seventy-eight Asian OTSCC cases were subjected to whole-exome and targeted deep sequencing. While the most common mutation seen was in TP53, the OTSCC genetic landscape differed from previously described cohorts of patients with head and neck squamous cell cancers: OTSCCs demonstrated frequent mutations in DST, FSIP2 and RNF213 while alterations in CDKN2A and NOTCH1 were significantly less frequent than previously reported. Despite a lack of previously-known NOTCH1 mutations, integrated analysis showed enrichments of alterations affecting Notch signaling, more commonly seen in women. Importantly, Notch pathway alterations were prognostic on uni- and multivariate analyses. Furthermore, a high proportion of OTSCCs presented with alterations in drug targetable genes and chromatin remodeling genes. Mutations in these groups were also prognostic, where patients harboring mutations in these actionable pathways more likely to succumb from recurrent disease compared to those who did not, suggesting that these patients should indeed be considered for treatment with targeted compounds in future trial designs. In conclusion, these findings define the mutational landscape of OTSCC, highlight the key role of the Notch signaling pathway in oral tongue tumorigenesis and uncover somatic mutations in therapeutically relevant genes which may represent candidate drug targets. Citation Format: Andre L. Vettore, Kalpana Ramnarayanan, Choon Kiat Ong, Hui Sun Leong, Weng Khong Lim, Ioana Cutcutache, John R. Mcpherson, Shenli Zhang, Thankshayeni Skanthakumar, Daniel SW Tan, Bin Tean Teh, Steve Rozen, Patrick Tan, N Gopalakrishna Iyer. Mutational landscapes of oral tongue squamous cell carcinoma reveal recurrent mutations in genes of therapeutic and prognostic relevance. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3874. doi:10.1158/1538-7445.AM2015-3874