Dataset Information

Rnaseq-22hcc - samples

ABSTRACT: RIKEN collection WGS and RNA-seq reads for 66 HBV-associated HCC and matched blood or liver samples from 22 donors.

PROVIDER: EGAD00001001035 | EGA |

REPOSITORIES: EGA

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Publications

Diverse modes of genomic alteration in hepatocellular carcinoma.

Jhunjhunwala Suchit S Jiang Zhaoshi Z Stawiski Eric W EW Gnad Florian F Liu Jinfeng J Mayba Oleg O Du Pan P Diao Jingyu J Johnson Stephanie S Wong Kwong-Fai KF Gao Zhibo Z Li Yingrui Y Wu Thomas D TD Kapadia Sharookh B SB Modrusan Zora Z French Dorothy M DM Luk John M JM Seshagiri Somasekar S Zhang Zemin Z

Genome biology 20140826 8

<h4>Background</h4>Hepatocellular carcinoma (HCC) is a heterogeneous disease with high mortality rate. Recent genomic studies have identified TP53, AXIN1, and CTNNB1 as the most frequently mutated genes. Lower frequency mutations have been reported in ARID1A, ARID2 and JAK1. In addition, hepatitis B virus (HBV) integrations into the human genome have been associated with HCC.<h4>Results</h4>Here, we deep-sequence 42 HCC patients with a combination of whole genome, exome and transcriptome sequenc ...[more]

PMID: 25159915

Publication: 1/2

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Project description:Chronic infections by hepatitis B virus (HBV) and hepatitis C virus (HCV) appear to be the most significant causes of hepatocellular carcinoma (HCC). Aberrant promoter methylation is known to be deeply involved in cancer, including HCC. In this study, we analyzed aberrant promoter methylation on genome-wide scale in 6 HCCs including 3 HBV-related and 3 HCV-related HCCs, 6 matched noncancerous liver tissues and 3 normal liver tissues by methylated DNA immunoprecipitation-on-chip analysis. Candidate genes with promoter methylation were detected more frequently in HCV-related HCC. Candidate genes methylated preferentially to HBV-related or HCV-related HCCs were detected and selected, and methylation levels of the selected genes were validated using 125 liver tissue samples, including 61 HCCs (28 HBV-related HCCs and 33 HCV-related HCCs) and matched 59 matched noncancerous livers, and 5 normal livers, by quantitative methylation analysis using MALDI-TOF mass spectrometry. Among analyzed genes, preferential methylation in HBV-related HCC was validated in 1 gene only. However, 15 genes were found methylated preferentially in HCV-related HCC, which was independent from age. Hierarchical clustering of HCC using these 15 genes stratified HCV-related HCC as a cluster of frequently methylated samples. The 15 genes included genes inhibitory to cancer-related signaling such as RAS/RAF/ERK and Wnt/b-catenin pathways. It was indicated that genes methylated preferentially in HCV-related HCC exist, and it was suggested that DNA methylation might play an important role in HCV-related HCC by silencing cancer-related pathway inhibitors. we analyzed aberrant promoter methylation in 6 HCC clinical samples (including 3 HBV-related HCCs and 3 HCV-related HCCs) and their matched noncancerous tissues on genome-wide scale by the method. Candidate regions of promoter methylation preferentially to HBV-related HCC and HCV-related HCC were selected, and the methylation levels of these genes were measured quantitatively using MALDI-TOF mass spectrometry. Expression levels of these 6 pairs of HCC and 4 more pairs of HCCs and surrounding noncancerous tissues were analyzed by expression array and are reported in this Series. <br><br>This experiment was reloaded in November 2010 after additional curation. this dataset is part of the TransQST collection.

Project description:The molecular mechanisms whereby hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC) remain elusive. We used genomic and molecular techniques to investigate host-virus interactions by mapping the entire liver of patients with HCC. We compared the gene signature of whole liver tissue (WLT) versus laser capture-microdissected (LCM) hepatocytes with intrahepatic expression of HBV. Gene expression profiling was performed on up to 17 WLT specimens obtained at various distances from the tumor center in individual livers of 11 patients with HCC and on selected LCM samples. HBV biomarkers were determined by real-time PCR and confocal immunofluorescence. Analysis of 5 areas of the liver showed a sharp change in gene expression between the immediate perilesional area and tumor periphery that correlated with a significant decrease in the intrahepatic expression of HBsAg. The tumor was characterized by a large preponderance of down-regulated genes, mostly involved in the metabolism of lipid and fatty acid, glucose, amino acids and drugs, with down-regulation of pathways involved in the activation of PXR/RXR and PPARa/RXRa nuclear receptors, comprising PGC1 and FOXO1, two key regulators of the hepatic metabolic functions and HBV transcription. These findings were confirmed by gene expression of microdissected hepatocytes. However, LCM of malignant hepatocytes also revealed up-regulation of unique genes associated with cancer and signaling pathways, including two novel HCC-associated cancer testis antigen (CTA) genes, NUF2 and TTK. HCC-associated with HBV is characterized by a metabolism switch-off and by a significant reduction in HBsAg. LCM proved to be a critical tool to validate gene signatures associated with HCC and to identify genes that may play a role in hepatocarcinogenesis opening new perspectives for the discovery of novel diagnostic markers and therapeutic targets. Samples were obtained at various distances from the tumor center in individual livers of 11 patients with HBV-associated HCC. Whole liver tissue samples were compared to LCM samples of malignant and non-malignant hepatocytes obtained from the same livers. This dataset is part of the TransQST collection.

Dataset Information

Rnaseq-22hcc - samples

Publications

Diverse modes of genomic alteration in hepatocellular carcinoma.

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