Document Detail


SIAH1 inactivation correlates with tumor progression in hepatocellular carcinomas.
MedLine Citation:
PMID:  12557228     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Koichi Matsuo; Seiji Satoh; Hiroshi Okabe; Akinari Nomura; Toshiki Maeda; Yoshio Yamaoka; Iwao Ikai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes, chromosomes & cancer     Volume:  36     ISSN:  1045-2257     ISO Abbreviation:  Genes Chromosomes Cancer     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-01-30     Completed Date:  2003-03-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9007329     Medline TA:  Genes Chromosomes Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  283-91     Citation Subset:  IM    
Copyright Information:
Copyright 2003 Wiley-Liss, Inc.
Affiliation:
Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. kmatsuo@kuhp.kyoto-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Carcinoma, Hepatocellular / genetics*,  pathology
Chromosome Deletion
Chromosome Mapping
Chromosomes, Human, Pair 16 / genetics
DNA Mutational Analysis
Databases, Genetic
Disease Progression
Female
Gene Expression Profiling
Gene Silencing*
Humans
Liver Neoplasms / genetics*,  pathology
Loss of Heterozygosity / genetics
Male
Middle Aged
Nuclear Proteins / antagonists & inhibitors*,  genetics*
Sequence Homology, Nucleic Acid
Tumor Cells, Cultured
Ubiquitin-Protein Ligases
Chemical
Reg. No./Substance:
0/Nuclear Proteins; EC 6.3.2.19/Ubiquitin-Protein Ligases; EC 6.3.2.19/seven in absentia proteins

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