Liver Tumours WGS
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001003446 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:The aim of this study is to define the mutational landscape of human liver tumours. .
This dataset contains all the data available for this study on 2020-02-20.
| EGAD00001005993 | EGA
Project description:Mutations and expression changes of epigenetic modifiers are pervasive in human tumours, making epigenetic factors attractive as antitumour targets. However, the mutational landscape of tumours correlates with the chromatin state of their cell-of-origin, raising the concern that targeting epigenetic factors might alter the mutational burden and possibly aggravate disease progression. Nonetheless, a causal link between changes in chromatin in tissues and the mutational landscape of their cognate tumours has not yet been established. Here we show that increasing chromatin accessibility through a conditional deletion of the histone H3K9 methyltransferase G9a severely delays and reduces carcinogen-induced squamous tumour initiation and burden. Strikingly, after a prolonged latency, G9a-mutant mice develop highly aggressive tumours with an expanded cancer stem cell (SC) pool. Loss of G9a leads to extensive chromatin opening in the cells of origin of these tumours (i.e. epidermal and hair follicle SCs) . Although this does not alter the number of single-nucleotide variants, the type of substitutions, or the overall mutational topography, it significantly changes the mutational signatures (i.e. microcontext) in the tumor cells. G9a-depleted tumours also display pronounced genomic instability and a frequent accumulation of loss-of-function p53 mutations, compared to their wild-type counterparts. Our results therefore provide evidence for a causal link between chromatin modifications and mutational load in tumours and call for caution when assessing the long-term therapeutic benefits of inhibiting epigenetic factors.
2018-11-13 | GSE99931 | GEO
Project description:Mutations and expression changes of epigenetic modifiers are pervasive in human tumours, making epigenetic factors attractive as antitumour targets. However, the mutational landscape of tumours correlates with the chromatin state of their cell-of-origin, raising the concern that targeting epigenetic factors might alter the mutational burden and possibly aggravate disease progression. Nonetheless, a causal link between changes in chromatin in tissues and the mutational landscape of their cognate tumours has not yet been established. Here we show that increasing chromatin accessibility through a conditional deletion of the histone H3K9 methyltransferase G9a severely delays and reduces carcinogen-induced squamous tumour initiation and burden. Strikingly, after a prolonged latency, G9a-mutant mice develop highly aggressive tumours with an expanded cancer stem cell (SC) pool. Loss of G9a leads to extensive chromatin opening in the cells of origin of these tumours (i.e. epidermal and hair follicle SCs) . Although this does not alter the number of single-nucleotide variants, the type of substitutions, or the overall mutational topography, it significantly changes the mutational signatures (i.e. microcontext) in the tumor cells. G9a-depleted tumours also display pronounced genomic instability and a frequent accumulation of loss-of-function p53 mutations, compared to their wild-type counterparts. Our results therefore provide evidence for a causal link between chromatin modifications and mutational load in tumours and call for caution when assessing the long-term therapeutic benefits of inhibiting epigenetic factors.
2018-11-13 | GSE99930 | GEO
Project description:Mutations and expression changes of epigenetic modifiers are pervasive in human tumours, making epigenetic factors attractive as antitumour targets. However, the mutational landscape of tumours correlates with the chromatin state of their cell-of-origin, raising the concern that targeting epigenetic factors might alter the mutational burden and possibly aggravate disease progression. Nonetheless, a causal link between changes in chromatin in tissues and the mutational landscape of their cognate tumours has not yet been established. Here we show that increasing chromatin accessibility through a conditional deletion of the histone H3K9 methyltransferase G9a severely delays and reduces carcinogen-induced squamous tumour initiation and burden. Strikingly, after a prolonged latency, G9a-mutant mice develop highly aggressive tumours with an expanded cancer stem cell (SC) pool. Loss of G9a leads to extensive chromatin opening in the cells of origin of these tumours (i.e. epidermal and hair follicle SCs) . Although this does not alter the number of single-nucleotide variants, the type of substitutions, or the overall mutational topography, it significantly changes the mutational signatures (i.e. microcontext) in the tumor cells. G9a-depleted tumours also display pronounced genomic instability and a frequent accumulation of loss-of-function p53 mutations, compared to their wild-type counterparts. Our results therefore provide evidence for a causal link between chromatin modifications and mutational load in tumours and call for caution when assessing the long-term therapeutic benefits of inhibiting epigenetic factors.
2018-11-13 | GSE99885 | GEO
Project description:Mutations and expression changes of epigenetic modifiers are pervasive in human tumours, making epigenetic factors attractive as antitumour targets. However, the mutational landscape of tumours correlates with the chromatin state of their cell-of-origin, raising the concern that targeting epigenetic factors might alter the mutational burden and possibly aggravate disease progression. Nonetheless, a causal link between changes in chromatin in tissues and the mutational landscape of their cognate tumours has not yet been established. Here we show that increasing chromatin accessibility through a conditional deletion of the histone H3K9 methyltransferase G9a severely delays and reduces carcinogen-induced squamous tumour initiation and burden. Strikingly, after a prolonged latency, G9a-mutant mice develop highly aggressive tumours with an expanded cancer stem cell (SC) pool. Loss of G9a leads to extensive chromatin opening in the cells of origin of these tumours (i.e. epidermal and hair follicle SCs) . Although this does not alter the number of single-nucleotide variants, the type of substitutions, or the overall mutational topography, it significantly changes the mutational signatures (i.e. microcontext) in the tumor cells. G9a-depleted tumours also display pronounced genomic instability and a frequent accumulation of loss-of-function p53 mutations, compared to their wild-type counterparts. Our results therefore provide evidence for a causal link between chromatin modifications and mutational load in tumours and call for caution when assessing the long-term therapeutic benefits of inhibiting epigenetic factors.
2018-11-13 | GSE99934 | GEO
Project description:Mutations and expression changes of epigenetic modifiers are pervasive in human tumours, making epigenetic factors attractive as antitumour targets. However, the mutational landscape of tumours correlates with the chromatin state of their cell-of-origin, raising the concern that targeting epigenetic factors might alter the mutational burden and possibly aggravate disease progression. Nonetheless, a causal link between changes in chromatin in tissues and the mutational landscape of their cognate tumours has not yet been established. Here we show that increasing chromatin accessibility through a conditional deletion of the histone H3K9 methyltransferase G9a severely delays and reduces carcinogen-induced squamous tumour initiation and burden. Strikingly, after a prolonged latency, G9a-mutant mice develop highly aggressive tumours with an expanded cancer stem cell (SC) pool. Loss of G9a leads to extensive chromatin opening in the cells of origin of these tumours (i.e. epidermal and hair follicle SCs) . Although this does not alter the number of single-nucleotide variants, the type of substitutions, or the overall mutational topography, it significantly changes the mutational signatures (i.e. microcontext) in the tumor cells. G9a-depleted tumours also display pronounced genomic instability and a frequent accumulation of loss-of-function p53 mutations, compared to their wild-type counterparts. Our results therefore provide evidence for a causal link between chromatin modifications and mutational load in tumours and call for caution when assessing the long-term therapeutic benefits of inhibiting epigenetic factors.
2018-11-13 | GSE99932 | GEO
Project description:Mutations and expression changes of epigenetic modifiers are pervasive in human tumours, making epigenetic factors attractive as antitumour targets. However, the mutational landscape of tumours correlates with the chromatin state of their cell-of-origin, raising the concern that targeting epigenetic factors might alter the mutational burden and possibly aggravate disease progression. Nonetheless, a causal link between changes in chromatin in tissues and the mutational landscape of their cognate tumours has not yet been established. Here we show that increasing chromatin accessibility through a conditional deletion of the histone H3K9 methyltransferase G9a severely delays and reduces carcinogen-induced squamous tumour initiation and burden. Strikingly, after a prolonged latency, G9a-mutant mice develop highly aggressive tumours with an expanded cancer stem cell (SC) pool. Loss of G9a leads to extensive chromatin opening in the cells of origin of these tumours (i.e. epidermal and hair follicle SCs) . Although this does not alter the number of single-nucleotide variants, the type of substitutions, or the overall mutational topography, it significantly changes the mutational signatures (i.e. microcontext) in the tumor cells. G9a-depleted tumours also display pronounced genomic instability and a frequent accumulation of loss-of-function p53 mutations, compared to their wild-type counterparts. Our results therefore provide evidence for a causal link between chromatin modifications and mutational load in tumours and call for caution when assessing the long-term therapeutic benefits of inhibiting epigenetic factors.
2018-11-13 | GSE99945 | GEO
Project description:Through the analysis of mouse liver tumours promoted by distinct routes (DEN exposure alone, DEN exposure plus non-genotoxic insult with phenobarbital and non-alcoholic fatty liver disease); we report that the cancer associated hyper-methylated CGI events in mice are also predicated by silent promoters that are enriched for both the DNA modification 5-hydroxymethylcytosine (5hmC) and the histone modification H3K27me3 in normal liver. During cancer progression these CGIs undergo hypo-hydroxymethylation, prior to subsequent hyper-methylation; whilst retaining H3K27me3. A similar loss of promoter-core 5hmC is observed in Tet1 deficient mouse livers indicating that reduced Tet1 binding at CGIs may be responsible for the epigenetic dysregulation observed during hepatocarcinogenesis. Consistent with this reduced Tet1 protein levels are observed in mouse liver tumour lesions. As in human, DNA methylation changes at CGIs do not appear to be direct drivers of hepatocellular carcinoma progression in mice. Instead dynamic changes in H3K27me3 promoter deposition are strongly associated with tumour-specific activation and repression of transcription. Our data suggests that loss of promoter associated 5hmC in diverse liver tumours licences DNA methylation reprogramming at silent CGIs during cancer progression. We carry out paired end , strand specific RNAseq prior to sequencing on Illumina Hiseq 2500 to report on the transcriptional landscape in replicate control mouse livers (n=2), 12 week Phenobarbital exposed livers (n=2)and resulting (35 week PB) liver tumours (n=3).
2016-05-17 | E-GEOD-77729 | biostudies-arrayexpress
Project description:Transcriptome profiles of C3H/HeJ mouse liver tumours
| PRJEB27617 | ENA
Project description:The aim of the proposed research is to develop a quick and reliable method for automated evaluation of tissue sections for residual tumour in histology specimens following liver surgery. This advanced technology will enable assessment of liver tumours and resection margins following liver surgery. The technology is based on Raman spectroscopy (RS) and multivariate spectral analysis to produce 2-dimensional biochemical images that can reliably separate the spectral signal of liver tumours from surrounding normal tissue.
| 70040 | ecrin-mdr-crc