Frequent frameshift mutations of RIZ in sporadic gastrointestinal and endometrial carcinomas with microsatellite instability

Many lines of evidence suggest that the retinoblastoma protein interacting zinc finger gene RIZ is a strong candidate for the tumor suppressor locus o n 1p36, a region commonly deleted in many human cancers with chromosomal in stability. In addition, a role for RIZ in tumors of the microsatellite inst ability pathway is suggested by frequent frameshift mutations in hereditary non-polyposis colorectal carcinomas. Here we studied RIZ mutations in spor adic cancers with microsatellite instability. Frameshift mutations in the t wo coding polyadenosine tracks of RIZ were found in 19 (48%) of 40 gastric carcinomas, 6 (33%) of 18 endometrial carcinomas, 14 (26%) of 51 of colorec tal carcinomas, and 7 (54%) of 13 cell lines. Eleven tumor tissues showed b iallelic inactivation of RIZ. In contrast, no frameshift mutations were fou nd in 70 microsatellite stable tumors. These results suggest an important r ole for RIZ in sporadic cancers with microsatellite instability.