Ontology highlight
ABSTRACT:
PROVIDER: PRJNA411908 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6077200_1.fastq.gz | Fastqsanger.gz | |||
| SRR6077200_2.fastq.gz | Fastqsanger.gz | |||
| SRR6077210_1.fastq.gz | Fastqsanger.gz | |||
| SRR6077210_2.fastq.gz | Fastqsanger.gz | |||
| SRR6077220_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 128 |
Similar Datasets
Project description:High-resolution liver cancer genomic profiling links etiology, epigenetic and mutation signatures
| PRJNA406882 | ENA
Project description:High-resolution liver cancer genomic profiling links etiology, epigenetic and mutation signatures [ChIP-Seq]
| PRJNA406884 | ENA
Project description:High-resolution liver cancer genomic profiling links etiology, epigenetic and mutation signatures [RNA-Seq]
| PRJNA406886 | ENA
Project description: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
2018-09-12 | GSE103729 | GEO
Project description: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
2018-09-12 | GSE103728 | GEO
Project description:Mitotic cell division increases tumour mutation burden and copy number load, predictive markers of the clinical benefit of immunotherapy. Cell division correlates also with genomic demethylation involving methylation loss in late-replicating partial methylation domains. Here we find that immunomodulatory pathway genes are concentrated in these domains and transcriptionally repressed in demethylated tumours with CpG island promoter hypermethylation. Global methylation loss correlated with immune evasion signatures independently of mutation burden and aneuploidy. Methylome data of our cohort (n = 60) and a published cohort (n = 81) in lung cancer and a melanoma cohort (n = 40) consistently demonstrated that genomic methylation alterations counteract the contribution of high mutation burden and increase immunotherapeutic resistance. Higher predictive power was observed for methylation loss than mutation burden. We also found that genomic hypomethylation correlates with the immune escape signatures of aneuploid tumours. Hence, DNA methylation alterations implicate epigenetic modulation in precision immunotherapy.
2019-08-02 | GSE135222 | GEO
Project description:Primary outcome(s): The detection rates of epigenetic heterogeneity in primary tumor and plasma from colorectal cancer patients with Methylation-sensitive high resolution melt(MS-HRM).
| 2636460 | ecrin-mdr-crc
Project description:Mitotic cell division increases tumour mutation burden and copy number load with a positive and inverse correlation, respectively, with the clinical benefit of immunotherapy. Markers of cell division correlate also with genomic demethylation involving methylation loss in late-replicating partial methylation domains. Here we find that immunomodulatory pathway genes are concentrated in these domains and transcriptionally repressed in demethylated tumours with CpG island promoter hypermethylation. Global methylation loss correlated with immune evasion signatures independently of mutation burden and aneuploidy. Methylome data of our cohort (n = 60) and a published cohort (n = 81) in lung cancer and a melanoma cohort (n = 40) consistently demonstrated that genomic methylation alterations counteract the contribution of high mutation burden and increase immunotherapeutic resistance. Higher predictive power was observed for methylation loss than mutation burden. We also found that genomic hypomethylation correlates with the immune escape signatures of aneuploid tumours. Hence, DNA methylation alterations implicate epigenetic modulation as a combination regimens for precision immunotherapy.
2019-07-31 | GSE119144 | GEO
Project description:Alpha-1 antitrypsin deficiency (AATD) liver disease is characterized by marked heterogeneity in presentation and progression, despite a common underlying gene mutation, strongly suggesting the involvement of other genetic and/or epigenetic modifiers. Variation in clinical phenotype has added to the challenge of detection, diagnosis, and testing of new therapies in patients with AATD. We examined the contribution of DNA methylation (5-methylcytosine [5mC]) to AATD liver disease heterogeneity because 5mC responds to environmental and genetic cues and its deregulation is a major driver of liver disease. Using liver biopsies from adults with early-stage AATD and the ZZ genotype, genome-wide 5mC patterns were interrogated. We compared DNA methylation among patients with early AATD, and among patients with normal liver, cirrhosis, and hepatocellular carcinoma derived from multiple etiologic exposures, and linked patient clinical/demographic features. Global analysis revealed significant genomic hypomethylation in AATD liver-impacting genes related to liver cancer, cell cycle, and fibrosis, as well as key regulatory molecules influencing growth, migration, and immune function. Further analysis indicated that 5mC changes are localized, with hypermethylation occurring within a background of genome-wide 5mC loss and with patients with AATD manifesting distinct epigenetic landscapes despite their mutational homogeneity. By integrating clinical data with 5mC landscapes, we observed that CpGs differentially methylated among patients with AATD disease are linked to hallmark clinical features of AATD (e.g., hepatocyte degeneration and polymer accumulation) and further reveal links to well-known sex-specific effects of liver disease progression. Conclusion: Our data reveal molecular epigenetic signatures within this mutationally homogeneous group that point to ways to stratify patients for liver disease risk.
2019-06-10 | GSE119100 | GEO
Project description:Within the clonal heterogeneity of a tumor, the co-measurement of both genomic and transcriptomic signatures in single cells is of fundamental importance to accurately assess how the genetic information, for instance a somatic mutation, is correlated with a transcriptomic and cancer-related phenotype. However, there is currently no microfluidics-based high-throughput assay available that allows this analysis. To resolve this, we developed a new method for concurrent sequencing of the transcriptome and targeted genomic regions (CORTAD-seq) within the same single cell on a microfluidic high-throughput platform. Its operation is simple, at moderate reagent cost, with excellent data quality and good accessibility for a broad scientific community. We implemented this new method to dissect the cellular consequences of mutations that result in resistance to targeted therapy. Using different tyrosine kinase inhibitor (TKI) resistant PC9 lung cancer cell lines as our study model, we detected signatures of TKI resistant genes as well as expansion of T790M mutation and EGFR amplification in the resistant cells. Interestingly, we identify transcriptomic characteristics for resistance that are not dependent on the presence of T790M, the most common resistance mutation in EGFR, indicating that phenotypically similar resistance scenarios can emerge without T790M mutation and other genomic alterations or epigenetic modifications are required for the manifestation of the resistance phenotype. Cumulatively, the application of this method allows accurate evaluation of the genomic and transcriptomic changes in cancer during development of drug resistance at single cell level in uncovering potential new biomarker and therapeutic targets in resistant cancer.
2019-03-23 | GSE112274 | GEO