title: [Genome-wide molecular screening for the identification of new targets in human hepatocellular carcinoma].
abstract: Molecular hepatocarcinogenesis represents a step-wise process which in most cases is associated with a well-defined chronic liver disease. By meta-analysis of classical comparative genomic hybridization (CGH) data an oncogenetic progression model could be generated (1q gain→ 8q gain → 4q loss → 16q loss → 13q loss). Array-based CGH allows the identification of etiology-dependent and independent genomic alterations. The Mouse Double Minute homologue 4 (MDM4) was shown to act as an oncogene of 1q32.1 gains in human hepatocellular carcinoma (HCC). Integration of genomic and epigenomic data facilitated the identification of tumor suppressor gene candidates in human HCC. For instance, Polo-like kinase 3 (PLK3) is frequently inactivated via promoter hypermethylation in combination with a loss of the second allele at 1p34.1. Both MDM4 overexpression and methylation-dependent inactivation of PLK3 represent potential targets for future therapeutic approaches.
authors.affiliation: Pathologisches Institut, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 224, 69120 Heidelberg. thomas.longerich@med.uni-heidelberg.de
authors.forename: T
authors.initials: T
authors.lastname: Longerich
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D018797:Cell Cycle Proteins; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020868:Gene Silencing; D016153:Genes, Suppressor; D055106:Genome-Wide Association Study; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D025521:Tumor Suppressor Proteins; D000097868:Polo-like Kinases
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; C482775:MDM4 protein, human; C486256:PLK3 protein, human; D000097868:Polo-like Kinases