PMID- 10595907 OWN - NLM STAT- MEDLINE DCOM- 19991228 LR - 20220310 IS - 0002-9440 (Print) IS - 0002-9440 (Linking) VI - 155 IP - 6 DP - 1999 Dec TI - Beta-catenin mutations are frequent in human hepatocellular carcinomas associated with hepatitis C virus infection. PG - 1795-801 AB - Hepatocellular carcinoma (HCC) is one of the most common fatal cancers worldwide. Hepatitis B virus and hepatitis C virus infections, exposure to aflatoxin, and excessive intake of alcohol have been identified as major risk factors. However, the molecular mechanisms underlying their development are still poorly understood. Recently, beta-catenin, one of the key components of the Wnt signaling pathway, has been found to be mutated in about 20% of HCCs, suggesting a role of the Wnt pathway in their development. In this study, we examined beta-catenin and APC mutations in 22 HCCs associated with HCV infection, using single-strand conformation polymorphism (SSCP) followed by direct DNA sequencing. beta-Catenin mutations were found in nine (41%) cases, but no APC mutations were found. beta-Catenin immunohistochemistry revealed nuclear accumulation of beta-catenin protein in all nine tumors with a beta-catenin mutation and two additional tumors without a mutation. These results suggest that activation of the Wnt signaling pathway by beta-catenin mutation contributes significantly to the hepatocellular carcinogenesis associated with HCV infection. FAU - Huang, H AU - Huang H AD - Unit of Molecular Pathology, International Agency for Research on Cancer (IARC), Lyon, France. FAU - Fujii, H AU - Fujii H FAU - Sankila, A AU - Sankila A FAU - Mahler-Araujo, B M AU - Mahler-Araujo BM FAU - Matsuda, M AU - Matsuda M FAU - Cathomas, G AU - Cathomas G FAU - Ohgaki, H AU - Ohgaki H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Adenomatous Polyposis Coli Protein) RN - 0 (CTNNB1 protein, human) RN - 0 (Cytoskeletal Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Trans-Activators) RN - 0 (Wnt Proteins) RN - 0 (Zebrafish Proteins) RN - 0 (beta Catenin) SB - IM MH - Adenomatous Polyposis Coli Protein MH - Aged MH - Carcinoma, Hepatocellular/*genetics/metabolism/pathology/*virology MH - Cytoskeletal Proteins/*genetics/metabolism MH - Female MH - Genes, APC MH - Hepatitis C/*complications MH - Humans MH - Immunohistochemistry MH - Liver Neoplasms/*genetics/metabolism/pathology/*virology MH - Male MH - Middle Aged MH - *Mutation MH - Polymorphism, Genetic MH - Polymorphism, Single-Stranded Conformational MH - Proto-Oncogene Proteins MH - Sequence Analysis, DNA MH - Signal Transduction MH - *Trans-Activators MH - Wnt Proteins MH - *Zebrafish Proteins MH - beta Catenin PMC - PMC1866943 EDAT- 1999/12/14 00:00 MHDA- 1999/12/14 00:01 CRDT- 1999/12/14 00:00 PHST- 1999/12/14 00:00 [pubmed] PHST- 1999/12/14 00:01 [medline] PHST- 1999/12/14 00:00 [entrez] AID - S0002-9440(10)65496-X [pii] AID - 10.1016/s0002-9440(10)65496-x [doi] PST - ppublish SO - Am J Pathol. 1999 Dec;155(6):1795-801. doi: 10.1016/s0002-9440(10)65496-x.