Melanoma Brain Metastasis Atlas [patient_cell_lines_RNA-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE200217 | GEO | 2022/07/06
REPOSITORIES: GEO
Similar Datasets
Project description:Bulk ATAC-seq on 24 patient-derived cell lines corresponding to 4 melanoma brain metastases (MBM) and 4 peripheral/extracranial melanoma metastses (ECM).
2022-07-06 | GSE205033 | GEO
Project description:We performed single-cell/nuclei RNA-sequencing (sc/snRNA-seq) of 22 treatment-naïve melanoma brain metastases (MBM; 5 samples using scRNA-seq and 17 snRNA-seq) from 21 patients and 10 treatment-naïve peripheral (extracranial) metastases (ECM; all snRNA-seq) from 10 patients. We performed matched spatial sequencing using SlideSeq2 (n=16) on 11 snRNA-seq samples.
2022-07-06 | GSE200278 | GEO
Project description:We performed single-cell/nuclei RNA-sequencing (sc/snRNA-seq) of 22 treatment-naïve melanoma brain metastases (MBM; 5 samples using scRNA-seq and 17 snRNA-seq) from 21 patients and 10 treatment-naïve extracranial (peripheral) metastases (MPM; all snRNA-seq) from 10 patients . In total, we recovered 145,555 cell transcriptomes in 32 samples including 73,369 cells from MBM and 72,186 from MPM.
2022-07-06 | GSE200218 | GEO
Project description:We performed matched TCR-seq and single-cell RNA-sequencing of 5 treatment-naïve melanoma brain metastases (MBM) from 5 individual patients.
2022-07-06 | GSE200215 | GEO
Project description:Melanomas are heterogeneous and adopt multiple transcriptional states that can confer an invasive phenotype and resistance to therapy. Little is known about the epigenetic drivers of these cell states, limiting our ability to regulate melanoma heterogeneity and tumor progression. Here we identify stress-induced HDAC8 activity as the driver of a transcriptional state that increased the formation of melanoma brain metastases (MBM). Exposure of melanocytes and melanoma cells to multiple different stresses led to HDAC8 activation, a switch to a gene expression signature associated with a neural crest-stem cell like state (NCSC) and the adoption of an amoeboid, invasive phenotype. This cell state enhanced the survival of melanoma cells under shear stress conditions and increased the formation of metastases in the brain. ATAC-Seq and ChIP-Seq analysis showed HDAC8 to alter chromatin structure by increasing H3K27ac and accessibility at c-Jun binding sites without changing global histone acetylation. The increased accessibility of Jun binding sites was paralleled by decreased H3K27ac and accessibility at MITF binding sites and loss of melanoma-lineage gene expression. Mass spectrometry-based acetylomics demonstrated that HDAC8 deacetylated the histone acetyltransferase (HAT) EP300 leading to its enzymatic inactivation. This, in turn, led to an increased binding of EP300 to Jun-transcriptional sites and decreased binding to MITF-transcriptional sites. Increased expression of EP300 decreased invasion and increased the sensitivity of melanoma cells to multiple stresses while inhibition of EP300 function increased invasion, resistance to stress and the development of MBM. We identified HDAC8 as a novel mediator of transcriptional co-factor inactivation and chromatin accessibility that increases MBM development.
2023-09-26 | PXD044471 | Pride
Project description:An improved understanding of the molecular pathogenesis of brain metastases, one of the most common and devastating complications of advanced melanoma, may identify and prioritize rational therapeutic approaches for this disease. In particular, the identification of molecular differences between brain and extracranial metastases would support the need for the development of organ-specific therapeutic approaches. Hotspot mutations, copy number variations (CNV), global mRNA expression patterns, and protein expression and activation, quantitatively analyzed by molecular inversion probe arrays, microarrays and reverse phase protein array (RPPA) were evaluated in pairs of melanoma brain metastases and extracranial metastases from patients who had undergone surgical resection for both types of tumors. Seventy-two samples from 52 brain (except for patient 01, who had a spinal cord metastasis) and extracranial metastases of melanoma were analyzed. Available biological replicates (different parts of the same tumor) were included.
2014-05-08 | E-GEOD-50493 | biostudies-arrayexpress
Project description:Brain metastases (BrMs) are a devastating complication of solid tumors with challenging clinical management. In this study, immunogenomic and digital spatial analyses were applied to interrogate the peripheral blood and tumor specimens derived from 53 unique patients with metastatic brain tumors originating from different solid tumors including melanoma, breast cancer, lung cancer and renal cell carcinoma. In the peripheral blood, lower levels of neutrophil -lymphocytes ratio (NLR) were detected at time of craniotomy in patients with melanoma-derived brain metastasis (MBM) vs. non-melanoma- derived brain metastasis (non-MBM). Independently from the primary tumor of derivation, patients with BrMs and increased NLR levels were characterized by shorter overall survival (OS) following craniotomy. In the tumor microenvironment (TME), molecular evaluations performed on FFPEs revealed higher expression of genes and mRNA signatures identifying NK cells, CD8 cells and B cells in MBM (n=13) vs. non-MBM brain metastasis (n=41). Focusing on CD8 cells, higher infiltration of CD8+ cells were observed in patients with MBM with longer OS following craniotomy. Spatial proteomic analysis further highlighted the infiltration of CD8+ cells, antigen presenting cells- (HLA-DR+, CD11c+, B2M+), agonists of T cell activity (CD137+, CD40+) and B cells (CD20+) enriched in MBM vs non-MBM. On the contrary, an increased expression of genes associated with neuro-development, cell- cell adhesion, neutrophil enrichment together with the increased infiltrations of cells promoting neuro-differentiation (Neun+, S100+), immune regulatory functions (CD25+, CD127+), and granulocytes aggregation (CD66b+) were observed in non-MBM vs. MBM. These findings highlight that the TME of BrMs plays a pivotal role in the pathogenesis and therapeutic resistance of BrMs derived from different solid tumors. Our results also suggest that distinct neuro-immune interplay may contribute to treatment resistance in BrMs.
2024-09-11 | GSE245467 | GEO
Project description:Stress-induced HDAC8 activity has been determined to be a driver of a neural crest stem cell (NCSC)-like transcriptional state that increased the formation of melanoma brain metastases (MBM). RNA-Seq experiments were performed against forced HDAC8 expressing cells and empty vector containing melanoma cells to determine differences in gene expression for the HDAC8-induced NCSC-like transcriptional state.
2023-09-26 | GSE218625 | GEO
Project description:An improved understanding of the molecular pathogenesis of brain metastases, one of the most common and devastating complications of advanced melanoma, may identify and prioritize rational therapeutic approaches for this disease. In particular, the identification of molecular differences between brain and extracranial metastases would support the need for the development of organ-specific therapeutic approaches. Hotspot mutations, copy number variations (CNV), global mRNA expression patterns, and protein expression and activation, quantitatively analyzed by mass-array genotyping, molecular inversion probe arrays, microarrays and reverse phase protein array (RPPA) were evaluated in pairs of melanoma brain metastases and extracranial metastases from patients who had undergone surgical resection for both types of tumors. Somatic copy number variation (CNV) in 47 melanoma brain metastases (BM, except for patient 01, who had a spinal cord metastasis) and extracranial metastases (EM) were analyzed by molecular inversion probe (MIP) array (Affymetrix OncoScan FFPE Express 2.0). DNA were extracted from regions with >70% viable tumor cells from formalin-fixed and paraffin-embedded (FFPE) tissues. Of the 47 tumor samples, 22 were matched BM and EM from the same patients. In addition, 24 DNA samples from normal tissues were included as diploid controls.
2014-05-08 | E-GEOD-50495 | biostudies-arrayexpress
Project description:Genome-wide DNA-methylation profiling of intra- and extracranial melanoma metastases. The goal of the study was to identify differences between methylomes of intra- and extracranial metastases. For each metastasis, FFPE material was used to extract genomic DNA from a punch biopsy of a marked metastasis area. The Illumina Infinium MethylationEPIC array was used for hybridization.
2023-01-18 | GSE203152 | GEO