Project description:To characterize the genetic alterations that instigate hepatitis C virus-induced hepatocellular carcinoma (HCC), we conducted an integrative genomic analysis of 103 HCCs. Most tumors harbored 1q gain, 8q gain or 8p loss, with occasional alterations in 13 additional chromosome arms. In addition to amplifications at 11q13 in 6 tumors, 4 tumors harbored focal gains at 6p21 incorporating VEGFA, which were confirmed in 4 of 113 HCC in an independent validation set. Strikingly, this locus overlapped with copy gains in 4 of 371 lung adenocarcinomas. Overexpression of VEGFA via 6p21 gain suggested a cell-nonautonomous mechanism of oncogene activation. Hierarchical clustering of gene expression among 91 tumors identified 5 classes, including ‘Wnt-CTNNB1’, ‘proliferation’ and ‘interferon-related’ gene classes. We also discovered a novel class defined by polysomy of chromosome 7, gains of which were associated with early tumor recurrence after resection. These findings reveal key alterations in HCC pathogenesis and implicate potential therapeutic targets. Keywords: disease state analysis 103 hepatocellular carcinomas and 95 adjacent cirrhotic, non-tumoral liver tissue were obtained at the time of surgical resection of orthotopic transplantation.
Project description:This SuperSeries is composed of the following subset Series: GSE9843: Gene expression profiling of 91 hepatocellular carcinomas with hepatitis C virus etiology, Samples with "vascular invasion: Yes/No" were included in the study. GSE20017: Gene Signature to Identify Vascular Invasion in Hepatocellular Carcinoma Refer to individual Series
Project description:To characterize the genetic alterations that instigate hepatitis C virus-induced hepatocellular carcinoma (HCC), we conducted an integrative genomic analysis of 103 HCCs. Most tumors harbored 1q gain, 8q gain or 8p loss, with occasional alterations in 13 additional chromosome arms. In addition to amplifications at 11q13 in 6 tumors, 4 tumors harbored focal gains at 6p21 incorporating VEGFA, which were confirmed in 4 of 113 HCC in an independent validation set. Strikingly, this locus overlapped with copy gains in 4 of 371 lung adenocarcinomas. Overexpression of VEGFA via 6p21 gain suggested a cell-nonautonomous mechanism of oncogene activation. Hierarchical clustering of gene expression among 91 tumors identified 5 classes, including 'Wnt-CTNNB1', 'proliferation' and 'nterferon-related' gene classes. We also discovered a novel class defined by polysomy of chromosome 7, gains of which were associated with early tumor recurrence after resection. These findings reveal key alterations in HCC pathogenesis and implicate potential therapeutic targets. Experiment Overall Design: 91 hepatocellular carcinomas were obtained at the time of surgical resection or orthotopic transplantation.
Project description:SNP array data from 125 hepatocellular carcinomas were used to detect recurrent copy number alterations. 99 hepatocellular carcinomas and 86 matched normal samples were analyzed with Illumina HumanCNV370-Duo v1.0 chips. 26 hepatocellular carcinomas and 26 matched normal samples were analyzed with Illumina HumanOmniExpress BeadChip.
Project description:SNP array data from 127 hepatocellular adenomas and carcinomas were used to detect recurrent copy number alterations. 48 tumors were analyzed with Illumina HumanCNV370-Duo v1.0 chips. 79 tumors were analyzed with Illumina HumanOmniExpress BeadChip.
Project description:Genome-wide DNA methylation profiling was performed in paired samples of non-cancerous liver tissue and the corresponding cancerous tissue obtained from patients with hepatitis virus-related hepatocellular carcinomas using the Illumina Infinium HumanMethylation450 Beadchip.
Project description:Study goal is to disclose features of gene expressio profile of non-cancerous liver-infiltrating lymphocytes of type C hepatitis patients with hepatocellular carcinomas and tumor-infiltrating lymphocytes of type C hepatitis patients with hepatocellular carcinomas. Keywords: gene expression profile, non-cancerous liver-infiltrating lymphocytes, tumor-infiltrating lymphocytes, type C hepatitis, hepatocellular carcinoma
