Skawran Britta, Steinemann Doris, Weigmann Anja, Flemming Peer, Becker Thomas, Flik Jakobus, Kreipe Hans, Schlegelberger Brigitte, Wilkens Ludwig
Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany.
Mod Pathol. 2008 May;21(5):505-16. doi: 10.1038/modpathol.3800998. Epub 2008 Feb 15.
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.
肝细胞癌和肝腺瘤的细胞遗传学研究显示，1号染色体长臂的增加是一个重要的鉴别因素。然而，尚无研究将这些扩增事件与基因表达进行比较。因此，我们对通过基于阵列的比较基因组杂交进行细胞遗传学特征明确的肿瘤进行了基因表达谱分析。对于这种方法，我们对24例肝细胞癌和8例肝腺瘤进行了分析，这些肿瘤通过基于阵列的比较基因组杂交进行了细胞遗传学特征分析。使用包含43,000个点的全基因组微阵列测定mRNA的表达谱。层次聚类分析将所有肝腺瘤与肝细胞癌区分开来。微阵列的显著性分析显示肝细胞癌中有722个基因表达失调。基因集富集分析检测到位于1q22 - 42染色体带的上调基因群，这些区域也是比较基因组杂交中最常获得的区域。微阵列显著性分析和基因集富集分析的比较将失调基因的数量缩小到18个，其中7个基因位于1q22（SCAMP3、IQGAP3、PYGO2、GPATC4、ASH1L、APOA1BP和CCT3）。在肝腺瘤中，位于11p15、11q12和12p13染色体带的26个基因上调。然而，这些染色体带在肝腺瘤中并未获得。表达分析和比较基因组杂交确定了1q扩增区域中的基因上调。这些结果可能有助于进一步缩小肝癌发生中候选驱动基因的数量。
