Detection of frameshift mutations of RIZ in gastric cancers with microsatellite instability

AIM:To study the frameshift mutations of the retinoblastomaprotein-interacting zinc finger gene RIZ in gastric cancerwith microsatellite instability,and to identify two codingpolyadenosine tracts of RIZ.METHODS:Frameshift mutations at (A)8and (A)9tracts ofRIZ were detected in 70 human gastric cancer (HGC)specimens by DHPLC and DNA sequencing.Microsatelliteinstability (MSI) status was assessed by two mononucleotidemarkers,BAT26 and BAT25,by means of denaturing high-performance liquid chromatography (DHPLC).RESULTS:In 70 HGC samples,8 (11.4%) were found positivefor instabilities at BAT26 and BAT25.In 7 of the 8 caseswith instabilities at both BAT26 and BAT25 (MSI-H),1 wasunstable at BAT26 but stable at BAT25.Frameshiff mutationswere identified in 4 (57.1%) of the 7 samples with MSI-Hin the (A)9tract of RIZ without mutations in the (A)8tract.In contrast,frameshift mutations were found in neither ofthe polyadenosine tracts in 63 samples of MSI-L or MSI stabletumors.Pro704 LOH detection in 4 cases with frameshiftmutations did not find LOH in these cases.CONCLUSION:Frameshift mutations of RIZ may play animportant role in gastric cancers with MSI.