Similar Datasets
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:High-resolution liver cancer genomic profiling links etiology, epigenetic and mutation signatures
| PRJNA406882 | ENA
Project description:Patients with chronic obstructive pulmonary disease (COPD) are still waiting for curative treatments. Considering its environmental cause, we hypothesized that COPD will be associated with altered epigenetic signaling in lung cells. We generated genome-wide DNA methylation maps at single CpG resolution of primary human lung fibroblasts (HLFs) across COPD stages. We show that the epigenetic landscape is markedly changed early in COPD, with DNA methylation changes occurring predominantly in regulatory regions. RNA sequencing of matched fibroblasts demonstrated dysregulation of genes involved in proliferation, DNA repair, and extracellular matrix organization. Data integration identified 110 candidate regulators of disease phenotypes that were linked to fibroblast repair processes using phenotypic screens. Our study provides high-resolution multi-omic maps of HLFs across COPD stages. We reveal novel transcriptomic and epigenetic signatures associated with COPD onset and progression and identify new candidate regulators involved in the pathogenesis of chronic lung diseases. The presence of various epigenetic factors among the candidates demonstrates that epigenetic regulation in COPD is an exciting research field that holds promise for novel therapeutic avenues for patients.
| S-SCDT-10_15252-EMBJ_2022111272 | biostudies-other
Project description:Aim: To profile DNA methylation changes of primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Materials & methods: Patients with: PBC, PSC with inflammatory bowel disease (IBD), PSC without IBD, and age-, sex-matched controls were profiled for methylomes of peripheral blood by reduced representation bisulfite sequencing. Differentially methylated CpG (DMC) and differentially methylated region (DMR) were detected and compared. Results: We identified consistently altered DMCs and DMRs across diseases with involvement in key pathways. Many similarities noted between two subtypes of PSC, interestingly few existed between PBC and PSC. DMRs were highly enriched with transcription factor binding. Top DMC changes were validated in liver tissue of an independent cohort. Conclusion: Methylome profiling provides insights to PBC and PSC.
| S-EPMC7506472 | biostudies-literature
Project description:Patients with chronic obstructive pulmonary disease (COPD) are still waiting for curative treatments. Considering its environmental cause, we hypothesized that COPD will be associated with altered epigenetic signaling in lung cells. We generated genome-wide DNA methylation maps at single CpG resolution of primary human lung fibroblasts (HLFs) across COPD stages. We show that the epigenetic landscape is changed early in COPD, with DNA methylation changes occurring predominantly in regulatory regions. RNA sequencing of matched fibroblasts demonstrated dysregulation of genes involved in proliferation, DNA repair, and extracellular matrix organization. Data integration identified 110 candidate regulators of disease phenotypes that were linked to fibroblast repair processes using phenotypic screens. Our study provides high-resolution multi-omic maps of HLFs across COPD stages. We reveal novel transcriptomic and epigenetic signatures associated with COPD onset and progression and identify new candidate regulators involved in the pathogenesis of chronic lung diseases. The presence of various epigenetic factors among the candidates demonstrates that epigenetic regulation in COPD is an exciting research field that holds promise for novel therapeutic avenues for patients.
| S-EPMC10267701 | biostudies-literature
Project description:BackgroundThe incidence of human papillomavirus-associated vulval neoplasia is increasing worldwide; yet the associated genetic changes remain poorly understood.MethodsWe have used single-nucleotide polymorphism microarray analysis to perform the first high-resolution investigation of genome-wide allelic imbalance in vulval neoplasia. Our sample series comprised 21 high-grade vulval intraepithelial neoplasia and 6 vulval squamous cell carcinomas, with paired non-lesional samples used to adjust for normal copy number variation.ResultsOverall the most common recurrent aberrations were gains at 1p and 20, with the most frequent deletions observed at 2q, 3p and 10. Copy-neutral loss of heterozygosity at 6p was a recurrent event in vulval intraepithelial neoplasia. The pattern of genetic alterations differed from the characteristic changes we previously identified in cutaneous squamous cell carcinomas. Vulval neoplasia samples did not exhibit gain at 5p, a frequent recurrent aberration in a series of cervical tumours analysed elsewhere using an identical protocol.ConclusionThis series of 27 vulval samples comprises the largest systematic genome-wide analysis of vulval neoplasia performed to date. Despite shared papillomavirus status and regional proximity, our data suggest that the frequency of certain genetic alterations may differ in vulval and cervical tumours.
| S-EPMC2844038 | biostudies-literature
Project description:Circulating tumor cells and disseminated tumor cells (DTCs) are of great interest because they provide a minimally invasive window for assessing aspects of cancer biology, including tumor heterogeneity, a means to discover biomarkers of disease behavior, and a way to identify and prioritize therapeutic targets in the emerging era of precision oncology. However, the rarity of circulating tumor cells and DTCs poses a substantial challenge to the consistent success in analyzing their molecular features, including genomic aberrations. Herein, we describe optimized and robust methods to reproducibly detect genomic copy number alterations in samples of 2 to 40 cells after whole-genome amplification with the use of a high-resolution single-nuclear polymorphism-array platform and refined computational algorithms. We have determined the limit of detection for heterogeneity within a sample as 50% and also demonstrated success in analyzing single cells. We validated the genes in genomic regions that are frequently amplified or deleted by real-time quantitative PCR and nCounter copy number quantification. We further applied these methods to DTCs isolated from individuals with advanced prostate cancer to confirm their highly aberrant nature. We compared copy number alterations of DTCs with matched metastatic tumors isolated from the same individual to gain biological insight. These developments provide high-resolution genomic profiling of single and rare cell populations and should be applicable to a wide-range of sample sources.
| S-EPMC4715223 | biostudies-literature
Project description:BACKGROUND: Several high-density oligonucleotide microarray platforms are available for genome-wide single nucleotide polymorphism (SNP) detection and microarray-based comparative genomic hybridisation (array CGH), which may be used to detect copy number aberrations in human tumours. As part of the EuroBoNeT network of excellence for research on bone tumours (eurobonet.eu), we have evaluated four different commercial high-resolution microarray platforms in order to identify the most appropriate technology for mapping DNA copy number aberrations in such tumours. FINDINGS: DNA from two different cytogenetically well-characterized bone sarcoma cell lines, representing a simple and a complex karyotype, respectively, was tested in duplicate on four high-resolution microarray platforms; Affymetrix Genome-Wide Human SNP Array 6.0, Agilent Human Genome CGH 244A, Illumina HumanExon510s-duo and Nimblegen HG18 CGH 385 k WG tiling v1.0. The data was analysed using the platform-specific analysis software, as well as a platform-independent analysis algorithm. DNA copy number was measured at six specific chromosomes or chromosomal regions, and compared with the expected ratio based on available cytogenetic information. All platforms performed well in terms of reproducibility and were able to delimit and score small amplifications and deletions at similar resolution, but Agilent microarrays showed better linearity and dynamic range. The platform-specific analysis software provided with each platform identified in general correct copy numbers, whereas using a platform-independent analysis algorithm, correct copy numbers were determined mainly for Agilent and Affymetrix microarrays. CONCLUSIONS: All platforms performed reasonably well, but Agilent microarrays showed better dynamic range, and like Affymetrix microarrays performed well with the platform-independent analysis software, implying more robust data. Bone tumours like osteosarcomas are heterogeneous tumours with complex karyotypes that may be difficult to interpret, and it is of importance to be able to well separate the copy number levels and detect copy number changes in subpopulations. Taking all this into consideration, the Agilent and Affymetrix microarray platforms were found to be a better choice for mapping DNA copy numbers in bone tumours, the latter having the advantage of also providing heterozygosity information.
| S-EPMC2929238 | biostudies-literature
Project description:Array-CGH is a powerful tool for the detection of chromosomal aberrations. The introduction of high-density SNP genotyping technology to genomic profiling, termed SNP-CGH, represents a further advance, since simultaneous measurement of both signal intensity variations and changes in allelic composition makes it possible to detect both copy number changes and copy-neutral loss-of-heterozygosity (LOH) events. We demonstrate the utility of SNP-CGH with two Infinium whole-genome genotyping BeadChips, assaying 109,000 and 317,000 SNP loci, to detect chromosomal aberrations in samples bearing constitutional aberrations as well tumor samples at sub-100 kb effective resolution. Detected aberrations include homozygous deletions, hemizygous deletions, copy-neutral LOH, duplications, and amplifications. The statistical ability to detect common aberrations was modeled by analysis of an X chromosome titration model system, and sensitivity was modeled by titration of gDNA from a tumor cell with that of its paired normal cell line. Analysis was facilitated by using a genome browser that plots log ratios of normalized intensities and allelic ratios along the chromosomes. We developed two modes of SNP-CGH analysis, a single sample and a paired sample mode. The single sample mode computes log intensity ratios and allelic ratios by referencing to canonical genotype clusters generated from approximately 120 reference samples, whereas the paired sample mode uses a paired normal reference sample from the same individual. Finally, the two analysis modes are compared and contrasted for their utility in analyzing different types of input gDNA: low input amounts, fragmented gDNA, and Phi29 whole-genome pre-amplified DNA.
| S-EPMC1557768 | biostudies-literature