The phosphatidylinositol 3-kinase signaling (PI3K) pathway is integral to cell growth, proliferation and survival, and is upregulated in multiple human cancers. Several oncogenes and tumor suppressors within this pathway are altered by mutation, amplification or deletion, and are currently being investigated as therapeutic targets. The pattern of dysregulation in this pathway differs among various cancers, and has not been comprehensively characterized in oral squamous cell carcinoma.

After institutional review board approval, fresh frozen tumor and matched normal tissues were obtained from 32 patients treated for oral cavity squamous cell carcinoma, and genomic DNA was extracted. Using high-throughput Sanger sequencing, the 23 component genes of the PI3K/Akt/mTOR pathway were comprehensively sequenced. Putative mutations identified by mutation detection software were validated on a second PCR and sequencing procedure. Array CGH was performed on the Agilent 1M microarray, and data analysis performed using the RAE method.

Component genes within the PI3K/Akt/mTOR pathway were comprehensively sequenced, including AKT1, AKT2, AKT3, AKTS1, AXL, AGAP2, MTOR, GBL, GOLPH3, RAPTOR, MUC1, PDPK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PTEN, RHEB, RICTOR, TSC1 and TSC2. Activating mutations were identified in PIK3CA in 2 of 32 (6.3%) specimens. No other genes harbored somatic mutations. DNA copy number gains and losses are described in detail.

In the first comprehensive mutational and copy number analysis of 23 component genes of the PI3K/Akt/mTOR pathway in cancer, we report a low prevalence of somatic mutations, and a higher frequency of copy number alteration in oral cancer specimens. In contrast to colorectal, breast, ovarian, brain and bladder cancers, mutation is not the primary source of activation of this pathway in oral cancers.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2222.