Tokumaru Yutaka, Nomoto Shuji, Jerónimo Carmen, Henrique Rui, Harden Susan, Trink Barry, Sidransky David
Head and Neck Cancer Research Division, Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA.
Oncogene. 2003 Oct 9;22(44):6954-8. doi: 10.1038/sj.onc.1206403.
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.
1号染色体的远端短臂在包括胃肠道癌在内的多种人类肿瘤中常发生缺失。此前在几种癌症中报道过视网膜母细胞瘤蛋白相互作用锌指基因（RIZ）1的基因改变，包括1p36处的杂合性缺失（LOH）、移码突变和启动子高甲基化。在本研究中，我们评估了30例原发性胃癌中的RIZ1，发现2例（6.7%）存在移码突变。此外，使用实时定量甲基化特异性PCR，在11例（37%）病例中检测到RIZ1启动子的甲基化。在所有11例甲基化病例中，第二个等位基因的失活是通过移码突变、LOH或启动子甲基化发生的。我们的结果表明，RIZ1是人类胃癌中失活的一个特定靶点。
