Abstract C123: Frameshift mutations of chromosome cohesion-related genes SGOL1 and PDS5B in gastric and colorectal cancers with high microsatellite instability.

Abstract

Abstract Background: Cohesin is a protein complex that regulates chromatid cohesion and plays roles in preventing aneuploidy and maintaining chromosomal stability. SGOL1 encodes a cohesin protector and PDS5B encodes a regulatory cohesion factor. Both SGOL1 and PDS5B are considered putative tumor suppressor genes. Purpose: Aim of this study was to explore whether SGOL1 and PDS5B genes are mutated and expressionally altered in gastric (GC) and colorectal cancers (CRC). Method: In a database, we found that both genes possessed mononucleotide repeats in coding sequences that could be mutation targets in cancers with microsatellite instability (MSI). We analyzed mutations in them in 91 GC and 100 CRC with high MSI (MSI-H) or stable MSI/low MSI (MSS/MSI-L) by single-strand conformation polymorphism analysis and DNA sequencing. We also analyzed SGOL1 and PDS5B expressions in the GC and CRC by immunohistochemistry. Results: Overall, we found 21 SGOL1 frameshift mutations in 21 cancers and 18 PDS5B frameshift mutations in 16 cancers. SGOL1 and PDS5B frameshift mutation were detected in 26.6% and 20.3% of MSI-H respectively, but not in MSS/MSI-L (0/112). In immunohistochemistry, losses of SGOL1 and PDS5B were identified in 19 - 47% of the GC and CRC irrespective of MSI status. The losses were more common in those with the frameshift mutations or MSI-H than those without the mutations or MSI-H. Conclusion: The data indicate that frameshift mutations of SGOL1 and PDS5B, and their losses may be a feature of GC and CRC with MSI-H. Also, the data suggest that these alterations might contribute to cancer pathogenesis by deregulating cohesin-related functions. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C123. Citation Format: Changhyeok An, Min Sung Kim, Jae Im Lee, Nam Jin Yoo, Sug Hyung Lee. Frameshift mutations of chromosome cohesion-related genes SGOL1 and PDS5B in gastric and colorectal cancers with high microsatellite instability. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C123.