Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA132429 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Large scale screening for fusion genes in sarcoma patient samples
| PRJNA186867 | ENA
Project description:We have utilized a version 2.0 of our Fusion gene microarray (version 1.0 described by PMID: 19152679 and GEO, GPL8078) to screen cancer cell lines for known fusion genes We assembled a comprehensive database of published fusion genes, including those which have been reported only in individual studies and samples, and fusion genes resulting from deep sequencing of cancer genomes and transcriptomes. From the total set of 548 fusion genes, we designed 197,846 unique oligonucleotides, targeting both chimeric transcript junctions as well as sequences internal to each of the fusion gene partners. We investigated the presence of fusion genes in a series of 67 cell lines originating from 15 different cancer types. Data from ten leukaemia cell lines with known fusion gene status were used to evaluate and calibrate an automated scoring algorithm. In five out of ten cell lines the correct fusion gene was the top most scoring hit, and one came second, all six passing a cut-off of 50 percent of theoretical maximum-score. Two additional fusion genes, BCAS4-BCAS3 from the MCF-7 breast cancer cell line and CCDC6-RET from the TPC-1 thyroid cancer cell line were validated as true positive fusion transcripts from the remaining 57 cell lines. A total of 67 cell lines from various cancer types were analysed for presence of known fusion genes
2011-02-10 | E-GEOD-24737 | biostudies-arrayexpress
Project description:We have utilized a version 2.0 of our Fusion gene microarray (version 1.0 described by PMID: 19152679 and GEO, GPL8078) to screen cancer cell lines for known fusion genes We assembled a comprehensive database of published fusion genes, including those which have been reported only in individual studies and samples, and fusion genes resulting from deep sequencing of cancer genomes and transcriptomes. From the total set of 548 fusion genes, we designed 197,846 unique oligonucleotides, targeting both chimeric transcript junctions as well as sequences internal to each of the fusion gene partners. We investigated the presence of fusion genes in a series of 67 cell lines originating from 15 different cancer types. Data from ten leukaemia cell lines with known fusion gene status were used to evaluate and calibrate an automated scoring algorithm. In five out of ten cell lines the correct fusion gene was the top most scoring hit, and one came second, all six passing a cut-off of 50 percent of theoretical maximum-score. Two additional fusion genes, BCAS4-BCAS3 from the MCF-7 breast cancer cell line and CCDC6-RET from the TPC-1 thyroid cancer cell line were validated as true positive fusion transcripts from the remaining 57 cell lines.
2011-02-10 | GSE24737 | GEO
Project description:Transcriptional lineage factors are a prominent class of essential genes in cancer, but the mechanisms that maintain lineage fidelity in advanced cancer clones, and whether lineage factor pathways could be broadly exploited for cancer therapy remain poorly understood. Here, we have used clear cell renal cell carcinoma (ccRCC) as a model to characterise the mechanisms that underlie lineage factor dependence in cancer. Through CRISPR/Cas9 loss-of-function screening and functional validation we find that loss of SMARCB1, a member of the SWI/SNF chromatin remodelling complex, can confer an advantage to ccRCC cells upon inhibition of the essential renal lineage factor PAX8. PAX8 inhibition resistant cells formed tumours with a dramatically altered histology showing neuroendocrine differentiation. Based on ATAC-seq and RNA-seq analysis, SMARCB1 inactivation leads to large-scale loss of kidney-specific epigenetic programmes, acquisition of a cellular state resembling that of rhabdoid tumours, and eventual activation of proliferative pathways. We show that these pathways are supported by the adoption of new transcriptional dependencies on IRF2, BHLHE40, and ZNFX1, factors that represent rare essential genes across different lineage-specific and oncogenic pathways, a principle validated in a large-scale CRISPR/Cas9 screening data set comprising hundreds of cancer cell lines. Thus, lineage factor requirements in cancer can switch upon challenge. The rules governing such lineage switching should be considered when designing novel lineage factor-targeted cancer therapies.
2023-07-19 | GSE183353 | GEO
Project description:Transcriptional lineage factors are a prominent class of essential genes in cancer, but the mechanisms that maintain lineage fidelity in advanced cancer clones, and whether lineage factor pathways could be broadly exploited for cancer therapy remain poorly understood. Here, we have used clear cell renal cell carcinoma (ccRCC) as a model to characterise the mechanisms that underlie lineage factor dependence in cancer. Through CRISPR/Cas9 loss-of-function screening and functional validation we find that loss of SMARCB1, a member of the SWI/SNF chromatin remodelling complex, can confer an advantage to ccRCC cells upon inhibition of the essential renal lineage factor PAX8. PAX8 inhibition resistant cells formed tumours with a dramatically altered histology showing neuroendocrine differentiation. Based on ATAC-seq and RNA-seq analysis, SMARCB1 inactivation leads to large-scale loss of kidney-specific epigenetic programmes, acquisition of a cellular state resembling that of rhabdoid tumours, and eventual activation of proliferative pathways. We show that these pathways are supported by the adoption of new transcriptional dependencies on IRF2, BHLHE40, and ZNFX1, factors that represent rare essential genes across different lineage-specific and oncogenic pathways, a principle validated in a large-scale CRISPR/Cas9 screening data set comprising hundreds of cancer cell lines. Thus, lineage factor requirements in cancer can switch upon challenge. The rules governing such lineage switching should be considered when designing novel lineage factor-targeted cancer therapies.
2023-07-19 | GSE183352 | GEO
Project description:Copy number profiling of 27 gastric cancer cell lines and 105 gastric tumor tissues. we hypothesized that a detailed fine-scale survey of genomic CNAs might reveal potential genes disrupted by fusion events in gastric cancer. We inferred the locations of likely chromosomal breakpoints by identifying regions where closely-spaced microarray probes exhibited striking transitions in copy number. 27 gastric cancer cell lines and 105 gastric tumor tissues were profiled by Agilent 244K microarray.
2010-12-31 | E-GEOD-22694 | biostudies-arrayexpress
Project description:Cancer cell line panels that incorporate genomic and pharmacologic screening data have become powerful tools for investigating the relationship between gene expression and drug response in human cancer research. Similar cell line panels of such a scale as the NCI60, CCLE, or GDSC do not currently exist in canine cancer research. Here we have assembled a canine cancer cell line panel of 29 cell lines representing multiple tumor types that have undergone gene expression profiling and have begun to be used for pharmacologic screening. RNA was extracted from drug naïve canine cancer cell lines and subjected to microarray analysis.
2015-12-18 | E-GEOD-76126 | biostudies-arrayexpress
Project description:Transcriptional profiling of estrogen receptor fusion genes in breast cancer cell lines
| PRJNA789898 | ENA
Project description:Rhabdomyosarcoma (RMS) is a pediatric soft tissue cancer with no precision therapy available for affected patients. We hypothesized that with a general paucity of known mutations in RMS, chromatin structural driving mechanisms are essential for tumor proliferation. Thus, we carried out high-depth in situ Hi-C in representative cell lines and patient-derived xenografts to understand chromatin architecture in each major RMS subtype. We report a comprehensive 3D chromatin structural analysis and characterization of fusion-positive (FP-RMS) and fusion-negative rhabdomyosarcoma (FN-RMS). We have generated spike-in in situ Hi-C chromatin interaction maps for the commonest FP-RMS and FN-RMS cell lines, and compared our data with patient derived xenograft (PDX) models. In our studies we uncover common and distinct structural elements in large Mb-scale chromatin compartments, tumor-essential genes within variable topologically associating domains, and unique patterns of structural variation. This study enables a comprehensive resource for contextualizing gene regulation events in RMS, and high-depth chromatin interactivity maps for identification of functionally critical chromatin domains in this tumor.
2023-06-13 | GSE215202 | GEO
Project description:Rhabdomyosarcoma (RMS) is a pediatric soft tissue cancer with no precision therapy available for affected patients. We hypothesized that with a general paucity of known mutations in RMS, chromatin structural driving mechanisms are essential for tumor proliferation. Thus, we carried out high-depth in situ Hi-C in representative cell lines and patient-derived xenografts to understand chromatin architecture in each major RMS subtype. We report a comprehensive 3D chromatin structural analysis and characterization of fusion-positive (FP-RMS) and fusion-negative rhabdomyosarcoma (FN-RMS). We have generated spike-in in situ Hi-C chromatin interaction maps for the commonest FP-RMS and FN-RMS cell lines, and compared our data with patient derived xenograft (PDX) models. In our studies we uncover common and distinct structural elements in large Mb-scale chromatin compartments, tumor-essential genes within variable topologically associating domains, and unique patterns of structural variation. This study enables a comprehensive resource for contextualizing gene regulation events in RMS, and high-depth chromatin interactivity maps for identification of functionally critical chromatin domains in this tumor.
2023-06-13 | GSE215172 | GEO