|
Status |
Public on Sep 12, 2018 |
Title |
High-resolution liver cancer genomic profiling links etiology, epigenetic and mutation signatures [RNA-Seq] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
Purpose: This study unravel the mechanisms that link viral infection and cancer Methods:Human HCC cell line and HCC liver FFPE samples from HCC patients from three etiology groups- HBV, HCV infection, or neither were taken to explore their genomic DNA in two aspects: The HCC genomic mutations within the exons of 224 candidate genes, frequently mutated in HCC, using SureSelect™ Target Enrichment System kit and the transient response of liver cells to HCV infection, in genome wide histone modifications and gene expression, as demonstrated by ChIP-Seq and RNA-Seq. Results:Mutational signature was explored by high-resolution targeted sequencing that detected low-frequency passenger mutations in 64 HCC samples from three etiology groups – HBV, HCV, or other. We identified novel distinct etiology-dependent regional mutations signatures. To explore the link between genomic signature and genome wide chromatin organization we studied the epigenetic changes occur following HCV infection. We demonstrated that HCV infection induces epigenetic changes that persist as "epigenetic signature" following virus eradication and reprogram host gene expression. High mutation rate associated with HCV etiology correlated with HCV-induced changes in epigenetic markers leading to closed chromatin. Conclusions:We present a new link between cancer causing mutagenesis, and increase in liver cancer predisposition in chronic HCV-infected individuals. The sequential events begin with HCV-specific epigenetic signature that in turn dictates a unique HCV-specific somatic mutational profile in HCC
|
|
|
Overall design |
Huh-7.5 cells were infected with HCV and ChIP-seq (at least 3 biological replicates were conducted.) and RNA-seq (6 biological replicates ) were done, all compared to non infected cells
|
|
|
Contributor(s) |
Gal-Tanamy M, Haviv I |
Citation(s) |
30698808 |
Submission date |
Sep 12, 2017 |
Last update date |
May 15, 2019 |
Contact name |
Assam El-Osta |
Organization name |
Baker Heart and Diabetes Institute
|
Lab |
Human Epigenetics
|
Street address |
75 Commercial Road
|
City |
Melbourne |
ZIP/Postal code |
3004 |
Country |
Australia |
|
|
Platforms (1) |
GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
Samples (18)
|
GSM2779885 |
RNA-seq from HCV infected cells repeat1 |
GSM2779886 |
RNA- seq from non-infected cells repeat 1 |
GSM2779887 |
RNA-seq from HCV infected cells repeat 2 |
GSM2779888 |
RNA- seq from non-infected cells repeat 2 |
GSM2779889 |
RNA-seq from HCV infected cells repeat 3 |
GSM2779890 |
RNA- seq from non-infected cells repeat 3 |
GSM2779891 |
RNA-seq from HCV infected cells repeat 4 |
GSM2779892 |
RNA- seq from non-infected cells repeat 4 |
GSM2779893 |
RNA-seq from HCV infected cells repeat 5 |
GSM2779894 |
RNA- seq from non-infected cells repeat 5 |
GSM2779895 |
RNA-seq from HCV infected cells repeat 6 |
GSM2779896 |
RNA- seq from non-infected cells repeat 6 |
GSM2779897 |
RNA-seq from HCV infected and cured cells repeat 1 |
GSM2779898 |
RNA-seq from control cells with treatment repeat 1 |
GSM2779899 |
RNA-seq from HCV infected and cured cells repeat 2 |
GSM2779900 |
RNA-seq from control cells with treatment repeat 2 |
GSM2779901 |
RNA-seq from HCV infected and cured cells repeat 3 |
GSM2779902 |
RNA-seq from control cells with treatment repeat 3 |
|
This SubSeries is part of SuperSeries: |
GSE103730 |
High-resolution liver cancer genomic profiling links etiology, epigenetic and mutation signatures |
|
Relations |
BioProject |
PRJNA406886 |
SRA |
SRP117316 |