American Head & Neck Society
Translational Research Meeting

April 21-22, 2015

AHNS Annual Meeting
April 22-23, 2015 during the
Combined Otolaryngology Spring Meetings

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Mutational Landscapes Of Oral Tongue Squamous Cell Carcinoma Reveal Recurrent Mutations In Genes Of Therapeutic And Prognostic Relevance

Presentation: S024
Topic: Late Breaking Hot Topics
Type: TRM
Date: Wednesday, April 22, 2015
Session: 4:30 PM - 6:00 PM
Authors: Andre Luiz Vettore, Kalpana Ramnarayanan, Gregory Poore, Choon Kiat Ong, Huang Kie Kyon, Hui Sun Leong, Chong Fui Teen, Kiat-Hong Lim, Weng Khong Lim, Ioana Cutcutache, John R Mcpherson, Yuka Suzuki, Shenli Zhang, Thakshayeni Skanthakumar, Weining Wang, Daniel Shao-Weng Tan, Byoung Chul Cho, Teh Bin Tean, Steve Rozen, Patrick Tan, N Gopalakrishna Iyer
Institution(s): Head and Neck Service, Department of Surgical Oncology, National Cancer Centre
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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. Here, we sought 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 was in TP53, the OTSCC genetic landscape differed from previously described cohorts of patients with head and neck tumors: OTSCCs demonstrated frequent mutations in DST, FSIP2 and RNF213, while alterations in CDKN2A and NOTCH1 were significantly less frequent. Despite a lack of previously reported NOTCH1 mutations, integrated analysis showed enrichments of alterations affecting Notch signaling in OTSCC. Importantly, these Notch pathway alterations were prognostic on multivariate analyses. A high proportion of OTSCCs also presented with alterations in drug targetable and chromatin remodeling genes. Patients harboring mutations in actionable pathways more likely to succumb from recurrent disease compared to those who did not, suggesting that the former should be considered for treatment with targeted compounds in future trials. Our study defines the Asian OTSCC mutational landscape, highlighting the key role of Notch signaling in oral tongue tumorigenesis. We also observed somatic mutations in multiple therapeutically relevant genes, which may represent candidate drug targets in this highly lethal tumor type.

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