Frameshift Mutations of Cadherin Genes DCHS2, CDH10 and CDH24 Genes in Gastric and Colorectal Cancers with High Microsatellite Instability

摘要

Cadherins (CDHs) are important in maintenance of cell adhesion and polarity, alterations of which contribute to tumorigenesis. Alterations of E-cadherin, a prototype CDH, have been reported in many cancers. However, alterations of unconventional CDHs, including CDH10, CDH24 and DCHS2 are largely unknown in cancers. Aim of this study was to explore whether CDH10, CDH24 and DCHS2 genes are mutated in gastric (GC) and colorectal cancers (CRC). In a public database, we found that CDH10, CDH24 and DCHS2 genes had mononucleotide repeats in the coding sequences that might be mutation targets in the cancers with microsatellite instability (MSI). We analyzed the mutations in 89 GC and 131 CRC (high MSI (MSI-H) or stable MSI/low MSI (MSS/MSI-L)) by single-strand conformation polymorphism analysis and DNA sequencing. We found six DCHS2, one CDH10 and one CDH24 frameshift mutations in them. All of the mutations were detected in cancers with MSI-H and there was a statistical difference in the frameshift mutation frequencies between the cancers with MSI-H (8/105) and MSS/MSI-L (0/115). The DCHS2 frameshift mutations were found in 8.8 % and 4.2 % of GC and CRC with MSI-H respectively. Our results show that unconventional CDH10, CDH24 and DCHS2 genes harbored frameshift mutations. These mutations might inactivate the cell adhesion-related functions and could be a feature of GC and CRC with MSI-H.