Cse1l, A 20q Gain Passenger That Drives Colorectal Adenoma To Carcinoma Progression

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Background ‘Driver genes’ are defined as genes that promote the tumorigenic process upon acquirement of somatic alterations. Gain of chromosome 20q is an important factor in the progression of colorectal adenomas to carcinomas. Previously we identified TPX2 and AURKA as two genes that drive 20q amplification in colorectal adenoma to carcinoma progression, based on correlation of mRNA and protein expression levels with 20q DNA copy number status while functionally influencing cancer processes. These findings are consistent with the hypothesis that the selection advantage imposed by 20q gain in colorectal adenoma to carcinoma progression is achieved by gain-of-function of multiple cancer-related genes at chromosome 20q, rather than affecting a single driver gene. In addition to TPX2 and AURKA, other 20q genes such as CSE1L may further contribute to tumor progression. Aim We here investigated whether CSE1L is another 20q located gene that drives colorectal adenoma to carcinoma progression, in a 20q gain-dependent manner. Methods Functional effects of CSE1L on cell viability, anchorage-independent growth and invasion were investigated upon gene knockdown using the SW480 colorectal cancer cell line. CSE1L protein expression levels were examined by immunohistochemical evaluation of tissue microarrays containing a series of colorectal adenoma and carcinoma samples, which were characterized by genome-wide (microarray-based) DNA and mRNA profiling. Results CSE1L knockdown affected cell viability and anchorage-independent growth. CSE1L mRNA expression levels correlated with chromosome 20q DNA copy number status. However, CSE1L protein expression was not associated with 20q gain, although its expression was increased in carcinomas compared to adenomas. Conclusion CSE1L appears to be a driver of colorectal tumor progression based on its functional effects combined with increased protein expression levels in carcinomas compared to adenomas. However, the lack of correlation between CSE1L protein expression levels and 20q DNA copy number status in colorectal adenoma to carcinoma progression implies that CSE1L is merely a passenger rather than a driver of chromosome 20q amplification, suggesting that CSE1L protein levels are subject to post-transcriptional regulation in a 20q gain-independent manner. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 109. doi:1538-7445.AM2012-109