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Relative spatial heterogeneity revealed by transcriptional profiling of multi-region high-grade glioma samples

ABSTRACT: Affymetrix GeneChip® Human Genome U133 Plus 2.0 Array profiling of 20 primary, multi-region high-grade glioma samples.

ORGANISM(S): Homo sapiens

PROVIDER: GSE62802 | GEO | 2015/12/31

SECONDARY ACCESSION(S): PRJNA265185

REPOSITORIES: GEO

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Relative spatial heterogeneity revealed by transcriptional profiling of multi-region high-grade glioma samples

Project description:Affymetrix GeneChipÂ® Human Genome U133 Plus 2.0 Array profiling of 20 primary, multi-region high-grade glioma samples. Total RNA was extracted from primary high-grade glioma samples and hybridized to GeneChipÂ® Human Genome U133 Plus 2.0 Array according to the manufacturer's instructions.

2015-12-31 | E-GEOD-62802 | biostudies-arrayexpress

Spatial architecture of high-grade glioma reveals tumor heterogeneity within distinct domains

Project description:High-grade gliomas are aggressive primary brain cancers with poor response to standard regimens, driven by immense heterogeneity. In isocitrate dehydrogenase (IDH) wild-type high-grade glioma (glioblastoma, GBM), increased intra-tumoral heterogeneity is associated with more aggressive disease. Recently, spatial technologies have emerged to dissect this complex heterogeneity within the tumor ecosystem by preserving cellular organization in situ. Here, we construct a high- resolution molecular landscape of GBM and IDH-mutant high-grade glioma patient samples to investigate the cellular subtypes and spatial communities that compose high-grade glioma using digital spatial profiling and spatial molecular imaging. This uncovered striking diversity of the tumor and immune microenvironment, that is embodied by the heterogeneity of the inferred copy- number alterations in the tumor. Reconstructing the tumor architecture revealed brain-intrinsic niches, composed of tumor cells reflecting brain cell types and microglia; and brain-extrinsic niches, populated by mesenchymal tumor cells and monocytes. We further reveal that cellular communication in these niches is underpinned by specific ligand-receptor pairs. This primary study reveals high levels of intra-tumoral heterogeneity in high-grade gliomas, associated with a diverse immune landscape within spatially localized regions.

2023-12-13 | GSE232469 | GEO

Comparison of the transcriptomic profiles of two human glioma cell lines, U87 and Glio6.

Project description:Using Affymetrix GeneChip® Human Genome U133 Plus 2.0 Array, we compared the gene expression profiles between the glioma cell lines U87 and Glio6, cultured at 3% of oxygene.

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Spatial architecture of high-grade glioma reveals tumor heterogeneity within distinct domains.

Project description:BackgroundHigh-grade gliomas (HGGs) are aggressive primary brain cancers with poor response to standard regimens, driven by immense heterogeneity. In isocitrate dehydrogenase (IDH) wild-type HGG (glioblastoma, GBM), increased intratumoral heterogeneity is associated with more aggressive disease.MethodsSpatial technologies can dissect complex heterogeneity within the tumor ecosystem by preserving cellular organization in situ. We employed GeoMx digital spatial profiling, CosMx spatial molecular imaging, Xenium in situ mapping and Visium spatial gene expression in experimental and validation patient cohorts to interrogate the transcriptional landscape in HGG.ResultsHere, we construct a high-resolution molecular map of heterogeneity in GBM and IDH-mutant patient samples to investigate the cellular communities that compose HGG. We uncovered striking diversity in the tumor landscape and degree of spatial heterogeneity within the cellular composition of the tumors. The immune distribution was diverse between samples, however, consistently correlated spatially with distinct tumor cell phenotypes, validated across tumor cohorts. Reconstructing the tumor architecture revealed two distinct niches, one composed of tumor cells that most closely resemble normal glial cells, associated with microglia, and the other niche populated by monocytes and mesenchymal tumor cells.ConclusionsThis primary study reveals high levels of intratumoral heterogeneity in HGGs, associated with a diverse immune landscape within spatially localized regions.

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Spatial immune heterogeneity of hypoxia-induced exhausted features in high-grade glioma.

Project description:The tumor immune microenvironment (TIME) in high-grade glioma (HGG) exhibits high spatial heterogeneity. Though the tumor core and peripheral regions have different biological features, the cause of this spatial heterogeneity has not been clearly elucidated. Here, we examined the spatial heterogeneity of HGG using core and peripheral regions obtained separately from the patients with HGG. We analyzed infiltrating immune cells by flow cytometry from 34 patients with HGG and the transcriptomes by RNA-seq analysis from 18 patients with HGG. Peripheral region-infiltrating immune cells were in vitro cultured in hypoxic conditions and their immunophenotypes analyzed. We analyzed whether the frequencies of exhausted CD8+ T cells and immunosuppressive cells in the core or peripheral regions are associated with the survival of patients with HGG. We found that terminally exhausted CD8+ T cells and immunosuppressive cells, including regulatory T (TREG) cells and M2 tumor-associated macrophages (TAMs), are more enriched in the core regions than the peripheral regions. Terminally exhausted and immunosuppressive profiles in the core region significantly correlated with the hypoxia signature, which was enriched in the core region. Importantly, in vitro culture of peripheral region-infiltrating immune cells in hypoxic conditions resulted in an increase in terminally exhausted CD8+ T cells, CTLA-4+ TREG cells, and M2 TAMs. Finally, we found that a high frequency of PD-1+CTLA-4+CD8+ T cells in the core regions was significantly associated with decreased progression-free survival of patients with HGG. The hypoxic condition in the core region of HGG directly induces an immunosuppressive TIME, which is associated with patient survival.

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Relative spatial homogeneity revealed by transcriptional profiling of multi-region medulloblastoma samples

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Spatial architecture of high-grade glioma reveals tumor heterogeneity within distinct domains

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Spatial genomic heterogeneity in multiple myeloma revealed by multi-region sequencing.

Project description:In multiple myeloma malignant plasma cells expand within the bone marrow. Since this site is well-perfused, a rapid dissemination of "fitter" clones may be anticipated. However, an imbalanced distribution of multiple myeloma is frequently observed in medical imaging. Here, we perform multi-region sequencing, including iliac crest and radiology-guided focal lesion specimens from 51 patients to gain insight into the spatial clonal architecture. We demonstrate spatial genomic heterogeneity in more than 75% of patients, including inactivation of CDKN2C and TP53, and mutations affecting mitogen-activated protein kinase genes. We show that the extent of spatial heterogeneity is positively associated with the size of biopsied focal lesions consistent with regional outgrowth of advanced clones. The results support a model for multiple myeloma progression with clonal sweeps in the early phase and regional evolution in advanced disease. We suggest that multi-region investigations are critical to understanding intra-patient heterogeneity and the evolutionary processes in multiple myeloma.In multiple myeloma, malignant cells expand within bone marrow. Here, the authors use multi-region sequencing in patient samples to analyse spatial clonal architecture and heterogeneity, providing novel insight into multiple myeloma progression and evolution.

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Relative spatial homogeneity revealed by transcriptional profiling of multi-region medulloblastoma samples

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