Published online May 28, 2015. doi: 10.3748/wjg.v21.i20.6317
Peer-review started: December 22, 2014
First decision: January 8, 2015
Revised: January 22, 2015
Accepted: March 12, 2015
Article in press: March 12, 2015
Published online: May 28, 2015
Core tip: Abnormal activation of Wnt/β-catenin signaling can be detected in approximately 50%-70% of hepatocellular carcinoma (HCC). It is necessary to take the analysis about the cause of Wnt/β-catenin signaling pathway aberration with the etiologic differences into consideration. In this review, the suggested genetic/epigenetic aberrations and their involvement in the abnormal Wnt/β-catenin overactivation in HCC were comprehensively analyzed, with focus on the cause of hepatitis B virus-related HCC. We suggest that genetic/epigenetic aberration of CTNNB1 and its protein degradation regulators are the major cause of Wnt signaling overactivation. TP53 gain-of-function mutation is seldom involved, and HBx-LINE1 chimeric transcripts created by viral integration may not be present.