title: Genetic alterations of Wnt signaling pathway-associated genes in hepatocellular carcinoma.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Recently, abnormal activation of the Wnt pathway has been found to be involved in the carcinogenesis of HCC. However, the relationship between genetic changes in the Wnt pathway-associated genes and its protein expression has not been studied in patients with HCC and cirrhotic nodules. The purpose of this study is to explore the contribution of inappropriate activation of the Wnt pathway in liver carcinogenesis.
  
  
  METHODS
  Somatic mutation in exons 3-5 of AXIN1 and exon 3 of beta-catenin were analyzed by direct sequencing and expression of axin and beta-catenin proteins by immunohistochemistry in a series of 36 patients with HCC and cirrhosis.
  
  
  RESULTS
  The AXIN1 and beta-catenin gene mutations were observed in 25% (9/36) and 2.8% (1/36) of HCCs, respectively. All mutations detected in AXIN1 and beta-catenin genes were missense point mutations. Abnormal nuclear expression of beta-catenin was observed in 11 of 36 cases of HCCs (30.6%), but not in cirrhotic nodules. Reduced or absent expression of axin was seen in 24 of 36 HCCs (66.7%). The abnormal expression of beta-catenin and axin proteins was closely correlated with mutations of AXIN1 and beta-catenin (P < 0.0001 and P = 0.008, respectively).
  
  
  CONCLUSIONS
  These data suggest that mutation of AXIN1 gene is a frequent and late event for HCC associated with cirrhosis, and is correlated significantly with abnormal expression of axin and beta-catenin. Therefore, activation of Wnt signaling through AXIN1 rather than beta-catenin mutation might play an important role in liver carcinogenesis.
authors.affiliation: Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea.
authors.forename: Young-Dae
authors.initials: YD
authors.lastname: Kim
authors.forename: Chang-Hwan
authors.initials: CH
authors.lastname: Park
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Sung-Kyu
authors.initials: SK
authors.lastname: Choi
authors.forename: Jong-Sun
authors.initials: JS
authors.lastname: Rew
authors.forename: Dong-Yi
authors.initials: DY
authors.lastname: Kim
authors.forename: Yang-Suk
authors.initials: YS
authors.lastname: Koh
authors.forename: Kyung-Woon
authors.initials: KW
authors.lastname: Jeung
authors.forename: Kyung-Hwa
authors.initials: KH
authors.lastname: Lee
authors.forename: Ji-Shin
authors.initials: JS
authors.lastname: Lee
authors.forename: Sang-Woo
authors.initials: SW
authors.lastname: Juhng
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D060466:Axin Protein; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D017354:Point Mutation; D012097:Repressor Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics
chemical_list: C555451:AXIN1 protein, human; D060466:Axin Protein; D012097:Repressor Proteins; D051153:Wnt Proteins; D051176:beta Catenin