Abstract Oral Squamous Cell Carcinoma (OSCC) - the subset of Head and Neck Cancer is the sixth most common cancer worldwide and leading cancer in India. Western part of India (Gujarat) is a prime tobacco growing belt, henceforth, has a high tobacco consumption and increased occurrence of oral cancer. Phosphatidylinositol- 3- kinase (PI3K) is heterodimeric protein kinase composed of catalytic subunit, p110α, and a regulatory subunit, p85α; which regulates cell proliferation, apoptosis, and metastasis. The PIK3CA gene, encodes p110α catalytic subunit, when somatically mutated gets highly deregulated in number of cancers. Canonical mutations E542K, E545K and H1047R in p110α have proven to have higher oncogenic potential, subsequently activating downstream pathways. However, this observation has been reported in limited ethnicity in OSCC. Therefore, we have analyzed mutation profile of exon9 and 20 of PIK3CA gene in 50 OSCC primary tumors and corresponding control samples by direct sequencing in Indian population. We have observed two hot spots mutations E542K and E545K in exon 9, which were earlier reported to activate downstream signaling pathways and two synonymous mutations C3075T and C2985T in exon 20 in fourteen and one OSCC patients, respectively. Patients harboring oncogenic mutations were at advanced stage of OSCC having tobacco chewing history more than ten years. Additionally, we observed two Single Nucleotide Polymorphism rs114587137 (C>T) and rs17849071 (T>G) in intron 9 of PIK3CA gene, which was found germ line mutated in fifteen and three OSCC patients respectively. In summary, we found 4% (2/50) oncogenic mutation frequency of PIK3CA gene, which may play a crucial role through PI3K downstream signaling pathway in oral neoplasia. Our study supports the notion that lower oncogenic mutation frequency of PIK3CA gene has been found in Asian populations but comparable to that seen in western countries. The knowledge of the involvement of PIK3CA mutations in OSCC is of importance, because a specific kinase inhibitor of PIK3CA may potentially serve as an effective therapeutic target against OSCC as a personalized medicine. Citation Format: Sejal Shah, Siddharth Shah, Harish Padh, Kiran Kalia. Mutational landscape of PIK3CA gene and its association with oral squamous cell carcinoma in Indian population. [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 581. doi:10.1158/1538-7445.AM2015-581
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