Methylation of osteosarcoma patients
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ABSTRACT:
PROVIDER: PRJNA678232 | ENA |
REPOSITORIES: ENA
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Project description:Osteosarcoma is the most common primary malignant tumour of bone occurring in children and young adolescents. Osteosarcoma is characterized by considerable phenotypic and genomic heterogeneity, and few recurrent targetable genetic changes have been reported. Osteosarcoma exhibits a complex karyotype with high genomic and chromosomal instability; and harbours multiple rearrangements across the genome, kataegis and chromothripsis as well as epigenetic changes. Here we have performed DNA methylation profiling on 10 osteosarcoma patient samples and four bones using the Infinium HumanMethylation450 BeadChip from Illumina, covering 485,000 CpG sites across the genome.
2022-01-31 | GSE161407 | GEO
Project description:Osteosarcoma is the most common primary malignant bone tumor in children. Validated markers for disease prognosis available at diagnosis are lacking. No genome-wide DNA methylation studies linked to clinical outcomes have been reported in osteosarcoma. To address this, we tested the methylome at over 1.1 million loci in 15 osteosarcoma biopsy samples obtained prior to the initiation of therapy and correlated these molecular data with disease outcomes. At the tested loci, samples obtained from patients who experienced disease relapse were generally more methylated than those from patients who did not have recurrence. In samples from patients who went on to have recurrent disease, increased DNA methylation was found at gene bodies, intergenic regions and empirically-annotated candidate enhancers, whereas candidate gene promoters were unusual for a more balanced distribution of increased and decreased DNA methylation. A locus at the TLR4 gene demonstrates one of strongest associations between DNA methylation and five year event-free survival, with empirical annotation of this locus showing promoter characteristics. Our data indicate that DNA methylation information has potential to be predictive of outcome in pediatric osteosarcoma, and that both promoters and non-promoter loci are potentially informative in DNA methylation studies. 15 samples. HpaII libraries were compared to at least 3 MspI libraries from the same sample
2015-01-18 | E-GEOD-59200 | biostudies-arrayexpress
Project description:Osteosarcoma is the most common primary malignant bone tumor in children. Validated markers for disease prognosis available at diagnosis are lacking. No genome-wide DNA methylation studies linked to clinical outcomes have been reported in osteosarcoma. To address this, we tested the methylome at over 1.1 million loci in 15 osteosarcoma biopsy samples obtained prior to the initiation of therapy and correlated these molecular data with disease outcomes. At the tested loci, samples obtained from patients who experienced disease relapse were generally more methylated than those from patients who did not have recurrence. In samples from patients who went on to have recurrent disease, increased DNA methylation was found at gene bodies, intergenic regions and empirically-annotated candidate enhancers, whereas candidate gene promoters were unusual for a more balanced distribution of increased and decreased DNA methylation. A locus at the TLR4 gene demonstrates one of strongest associations between DNA methylation and five year event-free survival, with empirical annotation of this locus showing promoter characteristics. Our data indicate that DNA methylation information has potential to be predictive of outcome in pediatric osteosarcoma, and that both promoters and non-promoter loci are potentially informative in DNA methylation studies.
2015-01-18 | GSE59200 | GEO
Project description:Background: Cellular apoptosis is a central mechanism the chemotherapy leveraged to treat human cancers. Cytosine methylations installed on both DNA and mRNA are documented to regulate apoptosis independently. However, the interplay or crosstalk between them in cellular apoptosis has not yet been explored. Methods: Cisplatin and doxorubicin were used to induce cell apoptosis in three differed types of osteosarcoma cell lines, respectively. Bisulfite-PCR, MS-PCR, and MeDIP experiments were employed to evaluate promoter cytosine methylation, and MeRIP were performed to investigate mRNA cytosine methylation. MeRIP-seq revealed the common target genes regulated by DNMT1 and NSun2. Particular chimeric reporter constructs were generated and dual luciferase assays dissected corresponding regulations via DNA and/or mRNA methylation. Cell viability assay, apoptosis analysis by flow cytometry, and tumor xenograft model were utilized to determine osteosarcoma drug resistance. Results: Promoter methylation by DNMT1 dialogues with mRNA methylation by NSun2 to coordinately regulate osteosarcoma cell apoptosis. DNMT1 was induced in osteosarcoma cell apoptosis triggered by chemotherapeutic drugs, whereas NSun2 expression was dampened. DNMT1 was found to represses NSun2 expression by methylating NSun2 promoter. Moreover, DNMT1 and NSun2 regulate anti-apoptotic genes AXL, NOTCH2, and YAP1 through DNA and mRNA methylation, respectively. Upon exposure to cisplatin or doxorubicin, DNMT1 elevation drastically reduced these anti-apoptotic gene expressions via enhanced promoter methylation coupled with NSun2 ablation-mediated attenuation of mRNA methylation, thus rendering osteosarcoma to apoptosis. Conclusions: Our findings establish a crosstalk of importance between DNA and RNA cytosine methylations in determining osteosarcoma resistance to apoptosis during chemotherapy, shedding new light on future treatment of osteosarcoma, and add additional layers to the control of gene expression at different epigenetic levels.
2025-06-01 | GSE205312 | GEO
Project description:Osteosarcoma is an aggressive tumor of the bone that primarily affects young adults and adolescents. Osteosarcoma is characterized by genomic chaos and heterogeneity. While inactivation of tumor suppressor p53 TP53 is nearly universal other high frequency mutations or structural variations have not been identified. Despite this genomic heterogeneity, key conserved transcriptional programs associated with survival have been identified across human, canine and induced murine osteosarcoma. The epigenomic landscape, including DNA methylation, plays a key role in establishing transcriptional programs in all cell types. The role of epigenetic dysregulation has been studied in a variety of cancers but has yet to be explored at scale in osteosarcoma. Here we examined genome-wide DNA methylation patterns in 24 human and 44 canine osteosarcoma samples identifying groups of highly correlated DNA methylation marks in human and canine osteosarcoma samples. We also link specific DNA methylation patterns to key transcriptional programs in both human and canine osteosarcoma. Building on previous work, we built a DNA methylation-based measure for the presence and abundance of various immune cell types in osteosarcoma. Finally, we determined that the underlying state of the tumor, and not changes in cell composition, were the main driver of differences in DNA methylation across the human and canine samples. Significance: This is the first large scale study of DNA methylation in osteosarcoma and lays the ground work for the exploration of DNA methylation programs that help establish conserved transcriptional programs in the context of different genomic landscapes.
2020-05-01 | GSE149679 | GEO
Project description:CDK4 overexpression is a predictive biomarker for resistance to conventional chemotherapy in osteosarcoma patients
2021-06-01 | GSE154540 | GEO
Project description:Osteosarcoma (OS) is a very aggressive bone tumor characterized by highly abnormal complex karyotypes.This a-CGH is a part of an expriment whose aim was to identify, genomic imbalance, DNA methylation and gene expression profiles in a panel osteosarcoma tumors. Keywords: comparative genomic hybridization
2009-09-08 | GSE12830 | GEO
Project description:DNA methylation in osteosarcoma and Ewing sarcoma
2020-01-13 | GSE125645 | GEO
Project description:Gene expression profiles of cultured mesenchymal stromal cells obtained from osteosarcoma patients at diagnosis and healthy donors were compared.
2015-06-30 | GSE42572 | GEO
Project description:Despite the development of diagnostic and advanced treatment strategies, the prognosis of patients with osteosarcoma remains poor. A limited understanding of the pathogenesis of osteosarcomas has impeded any improvement in patient outcomes over the past 4 decades. It is thus urgent to identify novel effective targets and treatment regimens for osteosarcoma patients. In this study we delineated the super-enhancer landscape in osteosarcoma cells on the basis of H3K27ac signal intensity by ChIP-Seq and found that super-enhancer-associated genes contribute to the malignant potential of osteosarcoma. THZ2, a novel small molecular inhibitor, shows a powerful anti-osteosarcoma ability through suppress super-enhancer-associated genes selectively. Utilizing the characteristics of super-enhancers in cancer cells, we identified 5 critical super-enhancer-associated oncogenes. With the comparative and retrospective analysis in large numbers of human specimens from patients, these 5 oncogenes were observed closely related with patient prognosis. Our findings determined that targeting super-enhancer-associated oncogenes with transcriptional inhibitor, THZ2, was a promising therapeutic strategy in osteosarcoma, and provided novel candidate targets for patients with osteosarcoma.
2019-12-27 | GSE134604 | GEO