Similar Datasets
Project description:Osteosarcoma (OS) is a primary malignant bone tumor commonly affecting children, adolescents, and young adults with a potential to metastasize to distal sites, most commonly lung. Here, we mapped the active chromatin landscapes of OS patients with varying extent of disease. We integrated histone H3 lysine acetylated chromatin (H3K27ac) profiles (n=13), chromatin accessibility profiles (n=11) and gene expression (n=13) of OS tumors from four different diseased states to understand the differences in their active chromatin profiles and its impact on molecular mechanisms driving the malignant phenotypes. Primary tumors that undergo metastasis (primary mets) have a distinct enhancer landscape compared to primary tumors that remain localized (localized) during the course of disease. The difference in chromatin activity shapes the transcriptional profile of OS patients. Some of the genes like PPP1R1B, PREX1 and IGF2BP1 whose role in OS pathogenesis and metastasis remains poorly understood, exhibit increased enhancer activity in primary mets along with higher RNA levels. Genome-wide loss-of-function screens also reveal these genes to be as selective dependencies in bone sarcomas, making them promising candidates for further investigation. Overall, differential chromatin activity in primary mets occurs in proximity of genes regulating actin cytoskeleton organization, cellular adhesion, and migration process suggestive of their role in facilitating OS metastasis. Thus, this data demonstrates that metastatic potential is intrinsically present in primary mets OS much before the occurrence of metastasis and when the cells are presented with favorable conditions to migrate and colonize at a distant site, they under undergo metastasis.
2023-12-09 | GSE234998 | GEO
Project description:Osteosarcoma (OS) is a primary malignant bone tumor commonly affecting children, adolescents, and young adults with a potential to metastasize to distal sites, most commonly lung. Here, we mapped the active chromatin landscapes of OS patients with varying extent of disease. We integrated histone H3 lysine acetylated chromatin (H3K27ac) profiles (n=13), chromatin accessibility profiles (n=11) and gene expression (n=13) of OS tumors from four different diseased states to understand the differences in their active chromatin profiles and its impact on molecular mechanisms driving the malignant phenotypes. Primary tumors that undergo metastasis (primary mets) have a distinct enhancer landscape compared to primary tumors that remain localized (localized) during the course of disease. The difference in chromatin activity shapes the transcriptional profile of OS patients. Some of the genes like PPP1R1B, PREX1 and IGF2BP1 whose role in OS pathogenesis and metastasis remains poorly understood, exhibit increased enhancer activity in primary mets along with higher RNA levels. Genome-wide loss-of-function screens also reveal these genes to be as selective dependencies in bone sarcomas, making them promising candidates for further investigation. Overall, differential chromatin activity in primary mets occurs in proximity of genes regulating actin cytoskeleton organization, cellular adhesion, and migration process suggestive of their role in facilitating OS metastasis. Thus, this data demonstrates that metastatic potential is intrinsically present in primary mets OS much before the occurrence of metastasis and when the cells are presented with favorable conditions to migrate and colonize at a distant site, they under undergo metastasis.
2023-12-09 | GSE234997 | GEO
Project description:Osteosarcoma (OS) is a primary malignant bone tumor commonly affecting children, adolescents, and young adults with a potential to metastasize to distal sites, most commonly lung. Here, we mapped the active chromatin landscapes of OS patients with varying extent of disease. We integrated histone H3 lysine acetylated chromatin (H3K27ac) profiles (n=13), chromatin accessibility profiles (n=11) and gene expression (n=13) of OS tumors from four different diseased states to understand the differences in their active chromatin profiles and its impact on molecular mechanisms driving the malignant phenotypes. Primary tumors that undergo metastasis (primary mets) have a distinct enhancer landscape compared to primary tumors that remain localized (localized) during the course of disease. The difference in chromatin activity shapes the transcriptional profile of OS patients. Some of the genes like PPP1R1B, PREX1 and IGF2BP1 whose role in OS pathogenesis and metastasis remains poorly understood, exhibit increased enhancer activity in primary mets along with higher RNA levels. Genome-wide loss-of-function screens also reveal these genes to be as selective dependencies in bone sarcomas, making them promising candidates for further investigation. Overall, differential chromatin activity in primary mets occurs in proximity of genes regulating actin cytoskeleton organization, cellular adhesion, and migration process suggestive of their role in facilitating OS metastasis. Thus, this data demonstrates that metastatic potential is intrinsically present in primary mets OS much before the occurrence of metastasis and when the cells are presented with favorable conditions to migrate and colonize at a distant site, they under undergo metastasis.
2023-12-09 | GSE234996 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-08-25 | E-GEOD-56255 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2015-08-25 | GSE56255 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-10-07 | GSE171447 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-01-13 | GSE138711 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2012-12-06 | E-GEOD-36004 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-12-18 | E-GEOD-76128 | biostudies-arrayexpress
Project description:Inactivation of the von Hippel-Lindau tumor suppressor gene, VHL, is an archetypical tumor-initiating event in clear cell renal carcinoma (ccRCC) that leads to the activation of hypoxia-inducible transcription factors (HIFs). However, VHL mutation status in ccRCC is not correlated with clinical outcome. Here we show that during ccRCC progression, cancer cells exploit diverse epigenetic alterations to empower a branch of the VHL-HIF pathway for metastasis, and the strength of this activation is associated with poor clinical outcome. By analyzing metastatic subpopulations of VHL-deficient ccRCC cells, we discovered an epigenetically altered VHL-HIF response that is specific to metastatic ccRCC. Focusing on the two most prominent pro-metastatic VHL-HIF target genes, we show that loss of polycomb repressive complex 2 (PRC2)-dependent histone H3 Lys27 trimethylation (H3K27me3) activates HIF-driven chemokine (C-X-C motif) receptor 4 (CXCR4) expression in support of chemotactic cell invasion, whereas loss of DNA methylation enables HIF-driven cytohesin 1 interacting protein (CYTIP) expression to protect cancer cells from death cytokine signals. Thus, metastasis in ccRCC is based on an epigenetically expanded output of the tumor-initiating pathway. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series.
2012-12-05 | E-GEOD-32299 | biostudies-arrayexpress