Genetic alterations in hepatoblastoma and hepatocellular carcinoma: common and distinctive aspects.
Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are two different subtypes of primary tumors arising from liver parenchymal cells. These tumors differ by many histoclinical characteristics, and comparative analysis of genetic alterations in HB and HCC might provide some clues on the molecular oncogenic pathways leading to hepatocyte transformation. Recent outcomes have been provided by the assessment of global genetic changes in tumor cells, using conventional cytogenetic approaches, PCR-based microsatellite analysis and Comparative genomic Hybridization (CGH). Cytogenetic studies of HB, microsatellite analysis of HCC and recent CHG data have outlined common and distinctive characters between the two tumor types. HBs are characterized by a low number of chromosomal changes, consisting mainly of gains at chromosomes 1q, 2, 8q, 17q, and 20. By contrast, HCCs harbor multiple chromosomal abnormalities, predominantly losses, with increased chromosomal instability in tumors associated with hepatitis B virus infection. Common alterations in HB and HCC include gain of chromosomes 1q, 8q, and 17q, and loss of 4q. Another important common feature shared by the two tumor types is the frequent activation of Wnt/beta-catenin signaling by stabilizing mutations of beta-catenin. Immunohistochemical analysis of beta-catenin has demonstrated nuclear/cytoplasmic accumulation of the protein in most HBs and in more than one third of HCCs. Strikingly, beta-catenin mutations are associated with chromosomal stability in both tumor types. Together, these studies define different pathways in liver cell transformation, reflecting various developmental stages and multiple risk factors. A detailed understanding of the molecular hits underlying liver tumorigenesis, combined with clinicopathological parameters, will permit an accurate evaluation of major targets for prognostic and therapeutic intervention.
Buendia
Marie Annick
MA
Unité de Recombinaison et Expression Génétique, Inserm U163, Département des Retrovirus, Institut Pasteur, Paris, France. mbuendia@pasteur.fr
D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics; D018197:Hepatoblastoma / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D015534:Trans-Activators / Q000235:genetics; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin