Abstract
Abstract Alternative splicing is a major source of protein diversity and cancer is driven by mutations in genes that control the proliferation of cells. The specific exon abnormality may contribute to the etiology of cancer and may provide selective drug targets. However, most studies of alternative splicing in human disease have used a targeted approach and focused on individual genes among whole genome. In this study, we evaluated an integrated approach of whole genome scale exon array and SNP array to detect cancer-associated alternative splicing, especially focusing on the protein kinase family. We investigated exon-level expression profiling against 22 gastric and colorectal cancer cell lines using Affymetrix Human Exon 1.0 ST Array. Array-based comparative genomic hybridization (CGH) analysis using high-density SNP Array (Affymetrix 250K Nsp /SNP6.0 Array) was also performed to explore genomic amplification/deletion. Several candidate alternative splicing or abnormalities of specific exon expression were detected in cancer-associated genes which detected genomic amplification/deletion frequently; exampling FGFR2, CDKN2A, and CDH13. We found the gene amplification of FGFR2 with C-terminus truncation. We also detected the existence of short CDH13 transcript resulted from small genomic deletion including consecutive 3 exons. In addition, exon-level expression pattern was compared between gastric and colorectal cancer cell lines. In conclusion, integration of whole genome exon array analysis and array CGH analysis may be a promising approach to explore the alternative exon abnormalities. 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 2156.
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