Genomic Landscape of Schwannoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE79009 | GEO | 2016/10/10
SECONDARY ACCESSION(S): PRJNA314718
REPOSITORIES: GEO
Similar Datasets
Project description:Cell state evolution underlies tumor development and response to therapy, but mechanisms specifying cancer cell states and intratumor heterogeneity are incompletely understood. Schwannomas are the most common tumors of the peripheral nervous system and are treated with surgery and ionizing radiation. Schwannomas can oscillate in size for many years after radiotherapy, suggesting treatment may reprogram schwannoma cells or the tumor microenvironment. Here we show epigenetic reprogramming shapes the cellular landscape of schwannomas. We find schwannomas are comprised of 2 methylation based molecular groups distinguished by reactivation of neural crest development pathways or misactivation of nerve injury mechanisms that specify cancer cell states and the architecture of the tumor immune microenvironment. Schwannoma molecular groups can arise independently, but ionizing radiation is sufficient for epigenetic reprogramming of neural crest to immune-enriched schwannoma by remodeling chromatin accessibility, gene expression, and metabolism to drive schwannoma cell state evolution and immune cell infiltration. To define functional genomic mechanisms underlying epigenetic reprograming of schwannomas, we develop a technique for simultaneous interrogation of chromatin accessibility and gene expression coupled with genetic and therapeutic perturbations in single-nuclei. Our results elucidate a framework for understanding epigenetic drivers of cancer evolution and establish a paradigm of epigenetic reprograming of cancer in response to radiotherapy.
2023-01-02 | GSE222042 | GEO
Project description:Cell state evolution underlies tumor development and response to therapy1, but mechanisms specifying cancer cell states and intratumor heterogeneity are incompletely understood. Schwannomas are the most common tumors of the peripheral nervous system and are treated with surgery and ionizing radiation2–5. Schwannomas can oscillate in size for many years after radiotherapy6,7, suggesting treatment may reprogram schwannoma cells or the tumor microenvironment. Here we show epigenetic reprogramming shapes the cellular landscape of schwannomas. We find schwannomas are comprised of 2 molecular groups distinguished by reactivation of neural crest development pathways or misactivation of nerve injury mechanisms that specify cancer cell states and the architecture of the tumor immune microenvironment. Schwannoma molecular groups can arise independently, but ionizing radiation is sufficient for epigenetic reprogramming of neural crest to immune-enriched schwannoma by remodeling chromatin accessibility, gene expression, and metabolism to drive schwannoma cell state evolution and immune cell infiltration. To define functional genomic mechanisms underlying epigenetic reprograming of schwannomas, we develop a technique for simultaneous interrogation of chromatin accessibility and gene expression coupled with genetic and therapeutic perturbations in single-nuclei. Our results elucidate a framework for understanding epigenetic drivers of cancer evolution and establish a paradigm of epigenetic reprograming of cancer in response to radiotherapy.
2023-04-18 | PXD014798 | Pride
Project description:Tumor heterogeneity in schwannoma
| PRJNA1530418 | ENA
Project description:Tumor heterogeneity in schwannoma
| PRJNA1530417 | ENA
Project description:Vestibular schwannoma (VS) is the most common benign tumor in the cerebellopontine angle and internal auditory canal. Illustrating the heterogeneous cellular components of VS could provide insights into its various growth patterns. Single-cell RNA sequencing (scRNA-seq) was used to profile transcriptomes from 7 VS samples and 2 great auricular nerves as normal control.
2024-03-13 | GSE230375 | GEO
Project description:Cerebrospinal fluid (liquor) samples (N = 44) have been derived from patients with vestibular schwannoma that comprises about 10% of all intracranial tumors. Applying high resolution tandem mass-spectrometry 525 proteins were identified with high confidence (at least 2 peptides per protein, FDR <1%) in the liquor samples. This dataset provides unique information on proteomic composition of vestibular schwannoma liquor samples.
2025-01-16 | PXD037746 | Pride
Project description:Wide methylation analysis in vestibular schwannoma
| PRJNA244045 | ENA
Project description:Proteomic analysis of the difference of protein expression between melanotic schwannoma and normal nerve
2024-03-11 | PXD050541 |
Project description:Vestibular Schwannoma (VS) is a benign tumor that arises from the Schwann cells of the VIII vestibulocochlear nerve. They contribute to 6-8% of the brain tumors and 80% of tumors originate from the cerebellopontine angle. Cystic vestibular schwannoma (cVS) represents 10% of vestibular schwannomas and are associated with an unpredictable growth behavior and poor surgical outcomes compared with solid vestibular schwannoma (sVS). Long non-coding RNAs (lncRNAs) belong to the class of non-coding RNAs and are known to regulate gene transcription and involved in chromatin remodeling via various mechanism. Despite accumulating evidence demonstrating the crucial roles of lncRNAs in multiple cancers, their comprehensive identification in cVS disease remains unknown. The objective of the current study was to identify lncRNAs associated with cVS using patient cohorts. Applying next generation sequencing, we performed whole transcriptome sequencing (RNA-seq) analysis and identified lncRNAs differentially expressed between cVS and sVS.
2026-07-31 | GSE278713 | GEO
Project description:Biallelic loss of the tumor suppressor NF2/merlin drives vestibular schwannomas (VS). Intratumoral heterogeneity has been observed in VS at the transcriptional, protein expression, and cellular proliferative potential levels, highlighting the need to elucidate the mechanisms underlying heterogeneity in tumor Schwann cell merlin inactivation and therapeutic resistance. Using integrated single-cell multi-omic profiling across NF2-related (VSnf2) and sporadic (VSspo) schwannomas, we identified functional merlin depletion as a continuous, spatially organized, plastic tumor Schwann cell state, rather than a binary genetic event. A transcriptomic merlin depletion score (MDS) captured this gradient, and merlin-depleted tumor Schwann cells were identified as a potential source of proliferative, angiogenic, and macrophage-recruiting signals. Lineage trajectory and multi-omic regulatory modeling identified the transcription factor TEAD1 as a potential regulator of MDS states and signaling pathways underlying tumor progression. Pharmacologic TEAD auto-palmitoylation inhibitors disrupted TEAD1–YAP/TAZ interactions, reversed merlin-loss transcriptional programs, suppressed VEGFA, NRG1, IL-34, and CSF1 signaling, and selectively attenuated tumor cell viability in human Schwann tumor cultures and in a mouse model. Overall, these findings show that merlin-loss heterogeneity is a functional, targetable axis in schwannoma and that TEAD1 inhibition could be a potentially useful therapeutic strategy for NF2/merlin depleted tumors.
2026-09-25 | GSE345131 | GEO