Genomics and signaling pathways in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a leading cause of death among cirrhotic patients and has become a major health problem in developed countries. There is an elemental understanding of the genes and signaling pathways involved in the initiation and progression of this neoplasm. The current hypothesis of the HCC cell origin includes both somatic cells (hepatocytes) and stem cells/progenitor cells. Unlike that in other malignancies such as breast, brain, or hematopoietic cancers, the implication of cancer stem cells in HCC pathogenesis is not yet supported by consistent data. Analysis of somatic genetic alterations and gene expression profiles in HCC samples has provided relevant information on the genes involved in hepatocarcinogenesis, pinpointing a seminal molecular classification of the disease. Nonetheless, a comprehensive genomic analysis of HCC samples using high-resolution platforms in precisely annotated HCCs is clearly needed. Recent data have identified different signaling pathways in liver carcinogenesis (e.g., Wnt-betaCatenin, Hedgehog, tyrosine kinase receptor-related pathways), providing an important potential source of novel molecular targets for new therapies. This review summarizes the most relevant information regarding structural and functional alterations in HCC and describes some of the key signaling pathways implicated in hepatocarcinogenesis.
Villanueva
Augusto
A
Mount Sinai Liver Cancer Program, Division of Liver Diseases, Mount Sinai School of Medicine, New York, New York 10029, USA.
Newell
Philippa
P
Chiang
Derek Y
DY
Friedman
Scott L
SL
Llovet
Josep M
JM
D022981:Allelic Imbalance; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D023281:Genomics; D053823:Hedgehog Proteins / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D051153:Wnt Proteins / Q000235:genetics
D053823:Hedgehog Proteins; D051153:Wnt Proteins; D020794:Receptor Protein-Tyrosine Kinases