Abstract 2149: Analysis of the cancer-specific correlation between genomic copy number aberration and gene expression in colorectal cancer

Abstract

Abstract Background: Recently, the technical innovation in molecular biological fields such as laser micro-dissection (LMD), cDNA microarray and array-based comparative genomic hybridization (array-CGH) have made it possible to analysis both genomic alteration and aberrant gene expression simultaneously at the level of cancer cell obtained from human cancer tissues. The aim of current study is to identify the novel genes to predict disease recurrence or prognosis with the concordant relationship between genomic alterations and aberrant gene expression during the progression of colorectal cancer (CRC). Materials and Methods: Candidate gene was found using cDNA microarray and array-CGH after LMD in 133 Japanese CRC. We picked up the several genes among the overexpressing genes with genomic amplification on the responsible loci in CRC. The expression of representative gene and its clinicopathlogical significance, including prognosis were evaluated another subset of 98 CRC cases. Results: We demonstrated that a correlation between chromosomal aberrations and gene expression in CRC was found in 8q, 13q and 20q. We identified 185 genes overexpressig in specific CRC cells among the genes on these chromosomes. We focused on SUGT1 (13q), which is associated with the assembling of kinetochore proteins at the metaphase of the cell cycle. SUGT1 mRNA expression was evaluated in 98 CRC cases to determine the clinicopathological significance of SUGT1 expression. The mean level of SUGT1 mRNA expression in tumor tissue specimens was significantly higher than in non-tumor tissue. The high SUGT1 expression group was characterized by a significantly elevated frequency of recurrence and a significantly poorer prognosis than the low expression group. Furthermore, SUGT1 expression was found to be a significant factor affecting five year overall survival following surgery in multivariate analysis (p = 0.04). Conclusion: We performed cDNA microarray and array-CGH analysis after LMD in a large scale study of Japanese CRC patients to identify new genomically amplified genes and determine the impact of their presence. Our results indicate that identified genes are not influenced by epigenetic alteration or microRNA. Furthermore, from a technical point of view, it is easier to handle genomic DNA than mRNA, as the latter is fragile, and unstable. Therefore, our findings suggest that this method of analysis might uncover additional genes indicative of patient prognosis and sensitivity to anticancer drugs. 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 2149.