Gene expression profiling in hepatocellular carcinoma: upregulation of genes in amplified chromosome regions

• Published in: Modern pathology 2008-05, Vol.21 (5), p.505-516
• Main Authors: Skawran, Britta, Steinemann, Doris, Weigmann, Anja, Flemming, Peer, Becker, Thomas, Flik, Jakobus, Kreipe, Hans, Schlegelberger, Brigitte, Wilkens, Ludwig
• Format: Article
• Language: English
• Subjects: Adenoma, Liver Cell - genetics; Adult; Aged; Carcinoma, Hepatocellular - genetics; Child; chromosomal instability; Chromosomes; Diagnosis, Differential; Female; Gene Amplification; Gene expression; Gene Expression Profiling; Genomes; Genomics; hepatocellular adenoma; hepatocellular carcinoma; Humans; Laboratory Medicine; Liver cancer; Liver Neoplasms - genetics; Male; Medical prognosis; Medical schools; Medicine; Medicine & Public Health; Middle Aged; Oligonucleotide Array Sequence Analysis; original-article; Pathology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Tumors; Up-Regulation
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.3800998

Cytogenetics of hepatocellular carcinoma and adenoma have revealed gains of chromosome 1q as a significant differentiating factor. However, no studies are available comparing these amplification events with gene expression. Therefore, gene expression profiling was performed on tumours cytogenetically well characterized by array-based comparative genomic hybridisation. For this approach analysis was carried out on 24 hepatocellular carcinoma and 8 hepatocellular adenoma cytogenetically characterised by array-based comparative genomic hybridisation. Expression profiles of mRNA were determined using a genome-wide microarray containing 43 000 spots. Hierarchical clustering analysis branched all hepatocellular adenoma from hepatocellular carcinoma. Significance analysis of microarray demonstrated 722 dysregulated genes in hepatocellular carcinoma. Gene set enrichment analysis detected groups of upregulated genes located in chromosome bands 1q22–42 seen also as the most frequently gained regions by comparative genomic hybridisation. Comparison of significance analysis of microarray and gene set enrichment analysis narrowed down the number of dysregulated genes to 18, with 7 genes localised on 1q22 (SCAMP3, IQGAP3, PYGO2, GPATC4, ASH1L, APOA1BP, and CCT3). In hepatocellular adenoma 26 genes in bands 11p15, 11q12, and 12p13 were upregulated. However, the respective chromosome bands were not gained in hepatocellular adenoma. Expression analysis and comparative genomic hybridisation identified an upregulation of genes in amplified regions of 1q. These results may serve to further narrow down the number of candidate driver genes in hepatocarcinogenesis.