Abstract 1216: Analysis of genetic aberrations in squamous cell carcinoma of the oral tongue.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Squamous cell carcinoma of the oral tongue (SCCOT) is a common form of head and neck squamous cell carcinoma (HNSCC). In the last few decades, a steady increase in incidence rates of SCCOT has been reported across the world including India. SCCOT is known to be an age related disease and tobacco consumption is implicated as the main etiological agent, like other HNSCC subtypes. Recent reports have indicated an increase in incidence of SCCOT in the young and in nonsmokers. Among HNSCC, SCCOT appears to be more aggressive with respect to its clinical and biological behavior. Molecular genetic studies on SCCOT are scarce and most studies have been conducted on a small cohort of patients and/or restricted to a single/few molecular marker(s). We have conducted a multipronged molecular genetic study of SCCOT and analyzed the status of known tumorigenesis pathways including TP53, epidermal growth factor receptor (EGFR), microsatellite instability (MSI), CDKN2A, FHIT and human papilloma virus (HPV) infection in surgically resected primary tumor samples and correlated with clinocopathological variables. 67% (67/100) of SCCOT samples exhibited p53 nuclear stabilization whereas a greater proportion (87/100; 87%) exhibited elevated EGFR expression, in accordance with existing literature. Interestingly, p53 nuclear stabilization was found to be more common in young (31/39; 79.5%) than in older (35/59; 59.3%) patients (p = 0.0481). As expected, patients with p53 nuclear stabilization exhibited poorer survival. Further, PCR based mutation screening of exons 5-8 of TP53 (encoding the DNA binding domain) revealed mutations in 50% of samples exhibiting nuclear stabilization. HPV infection was observed in 11/82 (13.4%) tumors while the frequencies of MSI (12/86; 14%) and loss of heterozygosity (LoH) in CDKN2A (32.6%) and FHIT (28.4%) loci were significantly higher than previous studies. In addition, LoH at FHIT locus was significantly associated with p53 nuclear stabilization (p=0.047). Analysis of genome-wide DNA copy number alterations (CNA) using array based comparative genomic hybridization revealed unique copy number alterations validated by quantitative PCR. Exome sequencing and transcriptome profiling are currently underway to understand the pathways/genes deregulated in SCCOT, especially in samples not exhibiting p53 nuclear stabilization. Citation Format: Raju Sr Adduri, Viswakalyan Kotapalli, Neha Ak Gupta, Swarnalata Gowrishankar, Mukta Srinivasulu, Subramanyeshwar Rao, Shantveer G. Uppin, Umanath Karopadi Nayak, Mohana Vamsy Chigurupati, Sujith Chayu Patnaik, NarasimhaRaju Kalidindi, Murali D. Bashyam. Analysis of genetic aberrations in squamous cell carcinoma of the oral tongue. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1216. doi:10.1158/1538-7445.AM2013-1216