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SIAH1 inactivation correlates with tumor progression in hepatocellular carcinomas
Author(s) -
Matsuo Koichi,
Satoh Seiji,
Okabe Hiroshi,
Nomura Akinari,
Maeda Toshiki,
Yamaoka Yoshio,
Ikai Iwao
Publication year - 2003
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.10170
Subject(s) - hccs , loss of heterozygosity , biology , hepatocellular carcinoma , cancer research , locus (genetics) , somatic cell , gene , microbiology and biotechnology , pathology , medicine , genetics , allele
Accumulation of loss of heterozygosity (LOH) on chromosome 16 is frequently observed in human hepatocellular carcinomas (HCCs). To identify tumor‐suppressor genes (TSGs) involved in hepatocarcinogenesis, we performed deletion mapping of chromosome 16 in 59 HCCs. Three commonly deleted regions, located in 16q12.1, 16q22.1, and 16q24.2, were observed. Because there has been no study on LOH at locus 16q12.1 in HCCs, we focused on this region. By searching the Human Genome Database at the National Center for Biotechnology Information web site, we identified 14 known genes in 16q12.1 as TSG candidates. Among these, the expression of SIAH1 was markedly downregulated in HCCs, and inactivation of SIAH1 expression was associated with LOH at 16q12.1. A mutation analysis of SIAH1 revealed no somatic mutations, but one single nucleotide polymorphism was found among the 35 HCCs investigated. Subsequently, we evaluated the relation between SIAH1 expression, confirmed by semiquantitative RT‐PCR, and clinicopathological parameters in HCCs. SIAH1 was significantly downregulated in advanced HCCs, including poorly differentiated tumors, larger tumors, and tumors in advanced stages. These findings suggest that inactivation of SIAH1 plays an important role in HCC progression. © 2003 Wiley‐Liss, Inc.