Biallelic inactivation of the RIZ1 gene in human gastric cancer

• DOI: 10.1038/sj.onc.1206403
• Publication Date: 2003-10-09T11:40:29Z
• Authors: Yutaka Tokumaru; Shuji Nomoto; Carmen Jerónimo; Rui Henrique; Susan Harden; Barry Trink; David Sidransky
• Keywords: Adult; Aged, 80 and over; Loss of Heterozygosity; Nuclear Proteins; Histone-Lysine N-Methyltransferase; DNA Methylation; Middle Aged; Retinoblastoma Protein; 3. Good health; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; 0302 clinical medicine; Chromosomes, Human, Pair 1; Stomach Neoplasms; Humans; Genes, Tumor Suppressor; Gene Silencing; Frameshift Mutation; Promoter Regions, Genetic; Alleles; Aged; Transcription Factors

The distal short arm of chromosome 1 is commonly deleted in a variety of human neoplasms including gastrointestinal cancer. Genetic alterations of the retinoblastoma protein-interacting zing-finger gene (RIZ)1 including loss of heterozygosity (LOH) at 1p36, frameshift mutations, and promoter hypermethylation were reported previously in several cancers. In this study, we evaluated RIZ1 in 30 primary gastric cancers and found frameshift mutations in two cases (6.7%). Moreover, using real-time quantitative methylation-specific PCR, methylation of the RIZ1 promoter was detected in 11 (37%) cases. In all 11 cases with methylation, inactivation of the second allele occurred through frameshift mutation, LOH or promoter methylation. Our results suggest that RIZ1 is a specific target of inactivation in human gastric cancer.