Abstract 2133: Identification of driver genes for amplification of the narrow amplicon at 2q11 present in oral cancers and pre-cancers

Abstract

Abstract Genome-wide analysis of copy number aberrations in oral squamous cell carcinoma (SCC) and oral epithelial dysplasia, a pre-malignant lesion, by array CGH has revealed that the genomes of these cancers and pre-cancers frequently harbor narrow (∼3 Mb) regions of amplification. These amplicons are recurrent, but rare, being present in <10% of cases. Nevertheless, candidate driver genes in the amplicon are often up-regulated in tumors without amplification. Thus, these narrow amplicons highlight genes/pathways that are de-regulated in oral cancer. A narrow amplicon at 2q11 has been observed in 3/44 oral dysplasia cases, in 1/89 oral SCC and one primary oral SCC cell line. In one patient with synchronous mild and moderate dysplasia lesions, the 2q11 amplicon was uniquely present in moderate dysplasia, suggesting that the amplified and overexpressed gene(s) at 2q11 contributed to progression. The 2q11 amplicon spans 3.5 Mb and includes 43 genes. Examination of two independent head and neck cancer gene expression datasets retrieved from the NCBI Gene Expression Omnibus database revealed up-regulation of 11 of these genes in one or both datasets. All 11 genes are overexpressed in oral SCC lines SCC4, SCC9 and HSC3. Knockdown of individual genes in a panel of eight oral SCC cell lines was performed with one or more siRNA's targeting each of the genes. These studies revealed that cellular proliferation and morphology were significantly disrupted in cells transfected with siRNA to two of the genes, suggesting there are two potential driver genes for the 2q11 amplicon. 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 2133.