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P53 gene and wnt signaling in benign Neoplasms: beta-Catenin mutations in hepatic adenoma but not in focal nodular hyperplasia
Author(s): Chen YW, Jeng YM, Yeh SH, Chen PJ
Source: HEPATOLOGY    Volume: 36    Issue: 4    Pages: 927-935    Part: Part 1    Published: OCT 2002  
Times Cited: 37     References: 48     
Abstract: Hepatocellular adenoma (HA) and focal nodular hyperplasia (FNH) arc 2 rare, benign liver neoplasms that often are discovered incidentally. To date, few genetic changes have been found in these 2 benign lesions. However, the 2 pathways of p53 and Wnt signaling, which may be the most common molecular targets involved in liver tumorgenesis, were studied in HA and FNH. Ten HAs and 11 FNHs were analyzed for loss of heterozygosity (LOH) and sequencing analysis of mutation hot spots in exons 5 to 8 of the p53 gene. No LOH or mutant sequences were identified, indicating that p53 was not associated with these benign lesions. Genes in the Wnt signaling pathway, including beta-catenin, axin, and adenomatous polyposis coli (APC), also were studied. Polymerase chain reaction (PCR) amplification and direct sequencing of all samples of HA and FNH displayed no mutations in exon 3 of the beta-catenin gene. However, 3 HAs (30%) contained interstitial deletions from exon 3 to exon 4. Truncated forms of beta-catenin detected by Western blot and immunohistochemical analyses showed they had accumulated in the cytoplasm and nuclei. However, for the axin and APC genes, no genetic changes, including allelic loss, interstitial deletions and point mutations, were detected in any of the HAs and FNHs. In conclusion, beta-catenin, which participates in the Wnt signaling pathway, might play a more important role in the formation of HA than in that of FNH, but p53 is not associated with the development of either HA or FNH.
Document Type: Article
Language: English
Reprint Address: Chen, PJ (reprint author), Natl Taiwan Univ Hosp, Hepatitis Res Ctr, 7 Chung Shan S Rd, Taipei 100, Taiwan
Addresses:
1. Natl Taiwan Univ Hosp, Hepatitis Res Ctr, Taipei 100, Taiwan
2. Natl Taiwan Univ, Grad Inst Mol Med, Taipei 10764, Taiwan
3. Natl Taiwan Univ, Dept Pathol, Coll Med, Taipei 10764, Taiwan
4. Natl Hlth Res Inst, Div Mol & Genomic Med, Taipei, Taiwan
Publisher: W B SAUNDERS CO, INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA
Subject Category: Gastroenterology & Hepatology
IDS Number: 598XE
ISSN: 0270-9139
DOI: 10.1053/jhep.2002.36126
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