Published online Nov 7, 2016. doi: 10.3748/wjg.v22.i41.9069
Peer-review started: August 19, 2016
First decision: September 6, 2016
Revised: September 20, 2016
Accepted: October 19, 2016
Article in press: October 19, 2016
Published online: November 7, 2016
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC.
Core tip: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. The poor survival rate is mainly due to late diagnosis of HCC. Elucidating the molecular mechanisms underlying hepatocarcinogenesis is critical for making early diagnoses of and developing targeted therapies for HCC. Recent studies on HCC using deep sequencing have provided increasing lines of evidence indicating that genetic alterations play important roles in the initiation and progression of HCC, which are summarized in this article. We also attempt to elucidate some of the genetic mechanisms underlying HCC, which may help in making early diagnoses of and developing molecularly targeted therapies for this disease.