Molecular and functional genetics of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the fifth most common cancer and one of the leading causes of cancer death worldwide. Hepatocarcinogenesis is a multistep process developing from normal through chronic hepatitis/cirrhosis and dysplastic nodules to HCC. Although we have insufficient understanding to propose a robust general model, with advances in molecular methods, there is a growing understanding of the molecular mechanisms in the development of HCC. Hepatocarcinogenesis is strongly linked to increases in allelic losses, chromosomal changes, gene mutations, epigenetic alterations, and alterations in molecular cellular pathways. Special emphasis in this review is given to the genetics, epigenetics, and regulation of major signaling pathways involved in HCC such as Wnt/b-catenin, Ras, and PI3K/Akt/mTOR pathways. A detailed understanding of the underlying molecular mechanisms involved in the progression of HCC can improve our prevention and diagnostic tools for HCC and be an important potential source of novel molecular targets for new therapies.
Yam
Judy Wai Ping
JW
Liver Cancer and Hepatitis Research Laboratory, Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
Wong
Chun Ming
CM
Ng
Irene Oi-Lin
IO
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000503:physiopathology*; D002869:Chromosome Aberrations; D044127:Epigenesis, Genetic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism; D000097202:ATP-Binding Cassette Sub-Family B Member 4
D018435:ATP Binding Cassette Transporter, Subfamily B; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051153:Wnt Proteins; D051176:beta Catenin; D018631:ras Proteins; D000097202:ATP-Binding Cassette Sub-Family B Member 4; C546842:MTOR protein, human; C546843:mTOR protein, mouse