Detection of frameshift mutations of RIZin gastric cancers with microsatellite instability

AIM. To study the frameshift mutations of the retinoblastoma protein-interacting zinc finger gene RIZin gastric cancer with microsatellite instability, and to identify two coding polyadenosine tracts of RIZ.METHODS: Frameshift mutations at (A)8 and (A)9 tracts of RIZ were detected in 70 human gastric cancer (HGC)specimens by DHPLC and DNA sequencing. Microsatellite instability (MSI) status was assessed by two mononucleotide markers, BAT26 and BAT25, by means of denaturing highperformance liquid chromatography (DHPLC).RESULTS: In 70 HGC samples, 8 (11.4%) were found positive for instabilities at BAT26 and BAT25. In 7 of the 8 cases with instabilities at both BAT26 and BAT25 (MSI-H), 1 was unstable at BAT26 but stable at BAT25. Frameshift mutations were identified in 4 (57.1%) of the 7 samples with MSI-H in the (A)9 tract of RlZwithout mutations in the (A)8 tract.In contrast, frameshift mutations were found in neither of the polyadenosine tracts in 63 samples of MSI-L or MSI stable tumors. Pro704 LOH detection in 4 cases with frameshift mutations did not find LOH in these cases.CONCLUSION: Frameshift mutations of RIZmay play an important role in gastric cancers with MSI.