P53 gene and Wnt signaling in benign neoplasms: beta-catenin mutations in hepatic adenoma but not in focal nodular hyperplasia.
Hepatocellular adenoma (HA) and focal nodular hyperplasia (FNH) are 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.
Chen
Ya-Wen
YW
Graduate Institute of Molecular Medicine, National Taiwan University, Taipei, Taiwan.
Jeng
Yung-Ming
YM
Yeh
Shiou-Hwei
SH
Chen
Pei-Jer
PJ
D018248:Adenoma, Liver Cell / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020518:Focal Nodular Hyperplasia / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin