| Microsatellite instability and alternative genetic pathway in intrahepatic cholangiocarcinoma. | |
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MedLine Citation:
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PMID: 11580146 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma (ICC) arises from intrahepatic bile duct epithelium and is the second most prevalent among primary liver cancers. The aim of this study was to clarify the mechanism of cholangiocarcinogenesis. METHODS: We studied the incidence of microsatellite instability (MSI) involving eight highly polymorphic microsatellite markers and alternations of the K-ras, p53 and mdm-2 genes in human ICC tissues. Overexpression of mdm-2 oncoprotein was also immunohistochemically studied. RESULTS: Of all 65 cases examined, K-ras gene mutation was found in three cases (4.6%) at codon 12. Analysis of p53 alterations was performed in 28 cases including 22 frozen samples and mutations were found in three cases (10.7%). Overexpression of mdm-2 protein was observed in 25 (41.7%) out of 60 cases analyzed. In 22 frozen samples, seven (31.8%) cases showed mdm-2 amplification and four (18.2%) cases revealed MSI-positive phenotype. Among the cases analyzed, all the tumors with mdm-2 amplification/overexpression harbored the wild-type p53 gene and all the microsatellite instability-positive cases were from mass-forming (MF) + periductal-infiltrating (PI) subtype. CONCLUSIONS: These results suggest that mdm-2 plays a role, which might be partially through inhibiting p53 activity, in cholangiocarcinogenesis and that M |
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Authors:
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H Momoi; T Itoh; Y Nozaki; Y Arima; H Okabe; S Satoh; Y Toda; E Sakai; K Nakagawara; P Flemming; M Yamamoto; Y Shimahara; Y Yamaoka; M Fukumoto |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of hepatology Volume: 35 ISSN: 0168-8278 ISO Abbreviation: J. Hepatol. Publication Date: 2001 Aug |
Date Detail:
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Created Date: 2001-10-02 Completed Date: 2002-03-25 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8503886 Medline TA: J Hepatol Country: Denmark |
Other Details:
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Languages: eng Pagination: 235-44 Citation Subset: IM |
Affiliation:
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Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Base Sequence Bile Duct Neoplasms / etiology, genetics*, metabolism, pathology Bile Ducts, Intrahepatic* Cholangiocarcinoma / etiology, genetics*, metabolism, pathology DNA, Neoplasm / genetics Female Gene Expression Genes, p53 Genes, ras Humans Immunohistochemistry Male Microsatellite Repeats* Middle Aged Mutation Nuclear Proteins* Polymorphism, Genetic Proto-Oncogene Proteins / genetics, metabolism Proto-Oncogene Proteins c-mdm2 |
| Chemical | |
Reg. No./Substance:
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0/DNA, Neoplasm; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins; EC 6.3.2.19/MDM2 protein, human; EC 6.3.2.19/Proto-Oncogene Proteins c-mdm2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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