Project description:We retrospectively identified adult patients who had received anti-PD-1 ICI therapy for recurrent sarcoma and performed DNA methylation profiling using Infinium MethylationEPIC microarrays. Response to anti-PD-1 ICI therapy was correlated with DNA methylation profiles.
Project description:DNA methylation classification reference set (1077) and validation set (428) of 1505 sarcoma samples using Illumina HumanMethylation450 BeadChips or Illumina Infinium HumanMethylation850 BeadChips
Project description:Developmental tumors in children and young adults carry few genetic alterations, yet they have diverse clinical presentation. Focusing on Ewing sarcoma, we sought to establish the prevalence and characteristics of epigenetic heterogeneity in genetically homogeneous cancers. We performed genome-scale DNA methylation sequencing for a large cohort of Ewing sarcoma tumors and analyzed epigenetic heterogeneity on three levels: between cancers, between tumors, and within tumors. We observed consistent DNA hypomethylation at enhancers regulated by the disease-defining EWS-FLI1 fusion protein, thus establishing epigenomic enhancer reprogramming as a ubiquitous and characteristic feature of Ewing sarcoma. DNA methylation differences between tumors identified a continuous disease spectrum underlying Ewing sarcoma, which reflected the strength of an EWS-FLI1 regulatory signature and a continuum between mesenchymal and stem cell signatures. There was substantial epigenetic heterogeneity within tumors, particularly in patients with metastatic disease. In summary, our study provides a comprehensive assessment of epigenetic heterogeneity in Ewing sarcoma and thereby highlights the importance of considering nongenetic aspects of tumor heterogeneity in the context of cancer biology and personalized medicine.
Project description:Genome wide DNA methylation profiling of Rhabdoid tumor of the kidney, Clear cell sarcoma of the kidney, Ewing's sarcoma family of tumors and non-neoplastic kidney. The Illumina Infinium HumanMethylation 27 BeadChip was used to obtain DNA methylation profiles across approximately 27000 CpGs . Samples included 3 Rhabdoid tumor of the kidney, 3 Clear cell sarcoma of the kidney, 3 Ewing's sarcoma family of tumor and 3 non-neoplastic kidney. Bisulfite converted DNA from the 12 samples were hybridized to the Illumina Infinium HumanMethylation27 Beadchip.
Project description:Genome wide DNA methylation profiling of Rhabdoid tumor of the kidney, Clear cell sarcoma of the kidney, Ewing's sarcoma family of tumors and non-neoplastic kidney. The Illumina Infinium HumanMethylation 27 BeadChip was used to obtain DNA methylation profiles across approximately 27000 CpGs . Samples included 3 Rhabdoid tumor of the kidney, 3 Clear cell sarcoma of the kidney, 3 Ewing's sarcoma family of tumor and 3 non-neoplastic kidney.
Project description:Infinium® HumanMethylation450 BeadChip and EPIC arrays were run with the aim of using the methylation profiles (n=986 in total) for sarcoma subtype classification (Paper: Lyskjær et al, 2021, DNA methylation-based profiling of bone and soft tissue tumours: a validation study of the ‘DKFZ sarcoma Classifier’ ). 500ng of DNA from fresh frozen (FT) or formalin-fixed paraffin-embedded (FFPE) tumour samples were bisulfite converted using the Zymo EZ DNA methylation Gold kit (Zymo Research Corp. Irvine, USA) before hybridisation to the Infinium HumanMethylation450 or EPIC beadchip arrays (Illumina, San Diego, CA) by UCL Genomics. All bisulfite-converted FFPE samples were restored with the Infinium FFPE DNA Restore kit (Illumina).
Project description:We performed reduced representation bisulfite seqeuncing (RRBS) and ChIP-seq of histone modification marks on three Ewing sarcoma tumor samples, and we quantified epigenetic heterogeneity on three levels. First, we identified a Ewing sarcoma specific hypomethylation signature at EWS-FLI1 regulated enhancers, showing that epigenetic enhancer reprogramming is a defining feature of Ewing sarcoma. Second, inter-individual DNA methylation differences in Ewing sarcoma samples identified a continuous disease spectrum with two dimensions: the strength of the EWS-FLI1 regulatory signature and the balance of mesenchymal versus stem cell regulatory signatures. Third, we observed substantial epigenetic heterogeneity within individual tumors. In summary, our study provides a comprehensive assessment of epigenetic heterogeneity in Ewing sarcoma, highlighting its importance as a source of variability for genetically homogeneous tumors.
Project description:Genome wide DNA methylation profiling of DNA extracted from formalin-fixed parffin embedded tumor samples from patients with primary intracranial sarcoma from Peru. The Illumina MethylationEPIC array was used to obtain DNA methylation profiles of 850.000 CpG sides
