Similar Datasets
Project description:We report DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, proteomic, and single-cell approaches to show meningiomas are comprised of 3 groups with distinct clinical outcomes, biological drivers, and therapeutic vulnerabilities. Merlin-intact meningiomas have the best outcomes and are distinguished by NF2/Merlin regulation of glucocorticoid signaling, apoptosis, and susceptibility to cytotoxic therapy. Immune-enriched meningiomas have intermediate outcomes and are distinguished by immune infiltration, HLA expression, and lymphatic vessels. Hypermitotic meningiomas have the worst outcomes and are distinguished by convergent genetic and epigenetic mechanisms driving the cell cycle and resistance to cytotoxic therapy. Our results establish a framework for understanding meningioma biology, and provide a foundation for new meningioma treatments.
2022-01-10 | GSE183647 | GEO
Project description:Meningiomas are the most common primary intracranial tumors. There are no effective medical therapies for meningioma patients, and new treatments have been encumbered by limited understanding of meningioma biology. Here, we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, proteomic and single-cell approaches to show meningiomas are composed of three DNA methylation groups with distinct clinical outcomes, biological drivers and therapeutic vulnerabilities. Merlin-intact meningiomas (34%) have the best outcomes and are distinguished by NF2/Merlin regulation of susceptibility to cytotoxic therapy. Immune-enriched meningiomas (38%) have intermediate outcomes and are distinguished by immune infiltration, HLA expression and lymphatic vessels. Hypermitotic meningiomas (28%) have the worst outcomes and are distinguished by convergent genetic and epigenetic mechanisms driving the cell cycle and resistance to cytotoxic therapy. To translate these findings into clinical practice, we show cytostatic cell cycle inhibitors attenuate meningioma growth in cell culture, organoids, xenografts and patients.
| S-EPMC9374001 | biostudies-literature
Project description:Meningioma DNA methylation grouping reveals biologic drivers and therapeutic vulnerabilities
| PRJNA761585 | ENA
Project description:Meningioma DNA methylation grouping reveals biologic drivers and therapeutic vulnerabilities (array)
| PRJNA761489 | ENA
Project description:DNA methylation from human meningioma samples that were also profiled for spatial heterogeneity analysis. Some samples represent spatially distinct regions, punched using a 2mm core punch from FFPE blocks in a given tumor. Other samples represent serial tumor samples at index treatment and then recurrence.
2023-06-14 | GSE228316 | GEO
Project description:AbstractCutaneous T-cell lymphoma (CTCL) is a rare cancer of skin-homing T cells. A subgroup of patients develops large cell transformation with rapid progression to an aggressive lymphoma. Here, we investigated the transformed CTCL (tCTCL) tumor ecosystem using integrative multiomics spanning whole-exome sequencing (WES), single-cell RNA sequencing, and immune profiling in a unique cohort of 56 patients. WES of 70 skin biopsies showed high tumor mutation burden, UV signatures that are prognostic for survival, exome-based driver events, and most recurrently mutated pathways in tCTCL. Single-cell profiling of 16 tCTCL skin biopsies identified a core oncogenic program with metabolic reprogramming toward oxidative phosphorylation (OXPHOS), cellular plasticity, upregulation of MYC and E2F activities, and downregulation of MHC I suggestive of immune escape. Pharmacologic perturbation using OXPHOS and MYC inhibitors demonstrated potent antitumor activities, whereas immune profiling provided in situ evidence of intercellular communications between malignant T cells expressing macrophage migration inhibitory factor and macrophages and B cells expressing CD74.SignificanceOur study contributes a key resource to the community with the largest collection of tCTCL biopsies that are difficult to obtain. The multiomics data herein provide the first comprehensive compendium of genomic alterations in tCTCL and identify potential prognostic signatures and novel therapeutic targets for an incurable T-cell lymphoma. This article is highlighted in the In This Issue feature, p. 1171.
| S-EPMC9148441 | biostudies-literature
Project description:DNA methylation profiling of human FFPE meningioma samples These samples were processed as part of a study developing and validating a targeted gene expression biomarker of meningioma outcomes and benefit from radiotherapy.
2023-09-06 | GSE221029 | GEO
Project description:Meningioma, one of the most common primary central nervous system tumors, are classified into three grades by the World Health Organization (WHO) based on histopathology. The gold-standard treatment, surgical resection, is hampered by issues such as incomplete resection in some cases and a high recurrence rate. Alongside genetic alterations, DNA methylation, plays a crucial role in progression of meningiomas in the occurrence and development of meningiomas. The epigenetic landscape of meningioma is instrumental in refining tumor classification, identifying robust molecular markers, determining prognosis, guiding treatment selection, and innovating new therapeutic strategies. Existing classifications lack comprehensive accuracy, and effective therapies are limited. Methylated DNA markers, exhibiting differential characteristics across varying meningioma grades, serve as invaluable diagnostic tools. Particularly, combinatorial methylated markers offer insights into meningioma pathogenesis, tissue origin, subtype classification, and clinical outcomes. This review integrates current research to highlight some of the most promising DNA and promoter methylation markers employed in meningioma diagnostics. Despite their promise, the development and application of DNA methylation biomarkers for meningioma diagnosis and treatment are still in their infancy, with only a handful of DNA methylation inhibitors currently clinically employed for meningioma treatment. Future studies are essential to validate these markers and ascertain their clinical utility. Combinatorial methylated DNA markers for meningiomas have broad implications for understanding tumor development and progression, signaling a paradigm shift in therapeutic strategies for meningiomas.
| S-EPMC10365284 | biostudies-literature
Project description: Not available
| S-EPMC11310866 | biostudies-literature
Project description:Glioblastoma (GBM) is one of the most aggressive types of cancer and exhibits profound genetic and epigenetic heterogeneity, making the development of an effective treatment a major challenge. The recent incorporation of molecular features into the diagnosis of patients with GBM has led to an improved categorization into various tumour subtypes with different prognoses and disease management. In this work, we have exploited the benefits of genome-wide multi-omic approaches to identify potential molecular vulnerabilities existing in patients with GBM. Integration of gene expression and DNA methylation data from both bulk GBM and patient-derived GBM stem cell lines has revealed the presence of major sources of GBM variability, pinpointing subtype-specific tumour vulnerabilities amenable to pharmacological interventions. In this sense, inhibition of the AP-1, SMAD3 and RUNX1/RUNX2 pathways, in combination or not with the chemotherapeutic agent temozolomide, led to the subtype-specific impairment of tumour growth, particularly in the context of the aggressive, mesenchymal-like subtype. These results emphasize the involvement of these molecular pathways in the development of GBM and have potential implications for the development of personalized therapeutic approaches.
| S-EPMC10483606 | biostudies-literature