Mapping of a minimal deleted region in human hepatocellular carcinoma to 1p36.13-p36.23 and mutational analysis of the RIZ (PRDM2) gene localized to the region

Abstract

Human chromosome band 1p36 commonly undergoes loss of heterozygosity (LOH) in hepatocellular carcinoma (HCC) but the minimal deleted region remains to be mapped. This chromosomal region contains a candidate HCC suppressor gene, RIZ (PRDM2), that is a member of the PR (PRDI-BFI-RIZ homology)-domain-containing zinc finger gene family. One characteristic of this family is the unusual yin-yang involvement in human cancers. The PR- domain-containing RIZI product of the RIZ locus, in contrast to the PR- domain-minus product RIZ2, is commonly lost or underexpressed in HCC. Furthermore, RIZI can induce cell cycle arrest, apoptosis, or both and suppress HCC tumorigenicity in nude mice. To help identify the putative HCC locus on 1p36 and to evaluate a genetic role of RIZ in HCC, we studied 97 HCC cases and mapped a minimal deleted region in HCC to 1p36.13-p36.23 between markers DIS434 and DIS436. Notably, RIZ mapped within this region and was found to undergo LOH in 37% (25/67) of HCC cases. Single-strand conformation polymorphism (SSCP) analysis, however, did not show mutations in the PR- domain region of RIZI in 49 cases of HCC examined. Our data suggest that the RIZ locus is a target of frequent deletion in HCC, but that the more common way of RIZ inactivation in HCC may not involve mutations that alter peptide sequences. (C) 2000 Wiley-Liss, Inc.