{"database": "metadata", "table": "run_metadata", "rows": [[70277, "SRR19641878", "SRX15691875", "SRS13388276", "SRP379972", "PRJNA848822", "VGLL2 NCOA2 leverages developmental programs for pediatric sarcomagenesis", "GSE206039", "Other", "Clinical sequencing efforts are rapidly identifying sarcoma gene fusions that lack functional validation. An example is the new fusion of transcriptional coactivators  VGLL2 NCOA2  found in infantile rhabdomyosarcoma. To delineate VGLL2 NCOA2 tumorigenic mechanisms and identify therapeutic vulnerabilities  we implemented a cross species comparative oncology approach with zebrafish  mouse allograft  and patient samples. We found that VGLL2 NCOA2 is sufficient to generate mesenchymal tumors that display features of immature skeletal muscle and recapitulate the human disease. A subset of VGLL2 NCOA2 zebrafish tumors transcriptionally cluster with embryonic somitogenesis and identify VGLL2 NCOA2 developmental targets  including a RAS family GTPase  arf6/ARF6. In VGLL2 NCOA2 zebrafish  mouse allograft  and patient tumors  arf6/ARF6 is highly expressed and is absent from mature skeletal muscle. Moreover  ARF6 is overexpressed in adult and pediatric sarcoma subtypes. Our data indicate that VGLL2 NCOA2 is an oncogene which leverages developmental programs for tumorigenesis  and that the reactivation or persistence of arf6/ARF6 could represent a therapeutic opportunity. Overall design: Examination of RNA seq transcriptional profiles from zebrafish tumors derived from mosaic human VGLL2 NCOA2 expression  and a comparison to mature  zebrafish skeletal muscle and CIC DUX4 generated zebrafish tumors. Examination of C2C12 mouse myoblasts stably transfected with human VGLL2 NCOA2  and allografted to generate tumor models. These are compared to allografts of C2C12 empty controls.", null, "pubmed:36656711", null, "Dr  D815", "GSM6239383", null, "source name:VGLL2 NCOA2 Tumor|tissue:VGLL2 NCOA2 Tumor|genotype:Wildtype AB/TL|age at sac:47 days|transgene:ptz876 cmv GFP2A VGLL2NCOA2 injected|cell line:n1|model:mosaic genetic tumor model", "Dr  D815", "Reads were trimmed with trim galore 0.6.4 and then trimmed to a maxiumum of 150bp Reads were aligned with STAR 2.7.2b against the zebrafish genome danRer11 or the mouse genome mm10 Reads per gene were counted using HTseq 0.12.4 and the outputs were merged within R Read counts were normalized in R using EdgeR All code used in processing is available at https://github.com/MVesuviusC/2022 VGLL2 NCOA2 paper Assembly: danRer11 or mm10 Supplementary files format and content: geneCountsCombinedDr norm.txt.gz and geneCountsCombinedDr norm.txt.gz are tables containing normalized gene counts", "VGLL2 NCOA2 Tumor", null, "For zebrafish  GFP positive and thus transgene positive tumors was extracted and flash frozen. Total RNA was isolated using the QIAGEN Rneasy Microkit. For zebrafish skeletal muscle total RNA was isolated with a QIAGEN Rneasy Minikit using an additional proteinase K step. For mouse allograft models total RNA was isolated using TRIZOL. RNA libraries were prepared for sequencing using standard Illumina protocols", "Here we describe transgenic zebrafish and mouse allograft models. For our transgenic zebrafish  Gateway cloning was performed to generate CMV GFP2A VGLL2NCOA2 and BetaActin GFP2A CICDUX4 injection constructs  each containing the human form of the fusion oncogene. These were injected into zebrafish in combination with Tol2 mRNA at the single cell stage  and fish were monitored for tumor formation. For our mouse allograft models  C2C12 cells were grown in DMEM+20% FBS  and were stably transfected with pcDNA3.1 control or pcDNA3.1 VGLL2NCOA2. Two million cells were injected intramuscularly to generate allograft VGLL2 NCOA2 tumor models.", "tissue:VGLL2 NCOA2 Tumor|genotype:Wildtype AB/TL|age at sac:47 days|transgene:ptz876 cmv GFP2A VGLL2NCOA2 injected|cell line:n1|model:mosaic genetic tumor model", "GSM6239383", "GSM6239383: Dr  D815; Danio rerio; RNA Seq", "GSM6239383 r1", "GSM6239383", "1", "For zebrafish  GFP positive and thus transgene positive tumors was extracted and flash frozen. Total RNA was isolated using the QIAGEN Rneasy Microkit. For zebrafish skeletal muscle total RNA was isolated with a QIAGEN Rneasy Minikit using an additional proteinase K step. For mouse allograft models total RNA was isolated using TRIZOL. RNA libraries were prepared for sequencing using standard Illumina protocols", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "ILLUMINA", "NextSeq 500", null, "SRP379972", null, "loader:fastq load.py", "D815.R1.fastq.gz D815.R2.fastq.gz", "fastq fastq", 5547049470.0, 37001650.0, "GSM6239383 r1", "0:75.00 1:74.91", "A:1493984328;C:1233438630;G:1231023373;T:1584983659;N:3619480", 75, 74, null, null, 1493984328, 1233438630, 1231023373, 1584983659, 3619480, "SRX15691875", "SRS13388276", null, null, "Kendall Lab, Nationwide Children's Hospital / The Ohio State University", 2, 0.93369, 0.93771, 0.12918, 0.12506, 0.73113, 0.73472, 0.51681, 0.5261, 76, 76, "B", "B", "biological fallback assumption", "illumina", "nextseq", "unknown", "cdna_unspecified", "unknown", "bulk", "unknown", "unknown", null, "United States", "2022-06-13", "Undetermined", "Embryo", "Cancer or Tumor", "Cancer or Tumor"]], "columns": ["rowid", "run.accession", "experiment.accession", "sample.accession", "study.accession", "bioproject", "study.title", "study.alias", "study.type", "study.abstract", "study.attributes", "study.PMIDs", "sample.description", "sample.title", "sample.alias", "sample.centername", "sample.attributes", "GEOsample.title", "GEOsample.dataprocessing", "GEOsample.source", "GEOsample.treatmentprotocol", "GEOsample.extractprotocol", "GEOsample.growthprotocol", "GEOsample.characteristics", "GEOsample.accession", "experiment.title", "experiment.alias", "experiment.library_name", "experiment.design_description", "experiment.library_construction_protocol", "experiment.attributes", "experiment.library_strategy", "experiment.library_source", "experiment.library_selection", "experiment.library_layout", "experiment.platform", "experiment.instrument_model", "experiment.spot_descriptor", "experiment.study_ref", "run.title", "run.attributes", "run.filename", "run.semantic_name", "run.total_bases", "run.total_spots", "run.alias", "run.read_lengths", "run.base_counts", "run.r1_length", "run.r2_length", "run.r3_length", "run.r4_length", "run.Acount", "run.Ccount", "run.Gcount", "run.Tcount", "run.Ncount", "run.experiment", "run.pool_member", "submission.accession", "submission.srasource", "submission.bioprojectsource", "seqdetective.n_mates", "seqdetective.mapping_rate.mate1", "seqdetective.mapping_rate.mate2", "seqdetective.nofeature_rate.mate1", "seqdetective.nofeature_rate.mate2", "seqdetective.sparsity.mate1", "seqdetective.sparsity.mate2", "seqdetective.pos_strand_rate.mate1", "seqdetective.pos_strand_rate.mate2", "seqdetective.readlen.mate1", "seqdetective.readlen.mate2", "seqdetective.judgement.mate1", "seqdetective.judgement.mate2", "seqdetective.judgement.reason", "platform_family", "instrument_generation", "read_bias", "selection_class", "prep_kit", "sc_or_bulk", "tech_class", "technology", "tech_variant", "submission.bioprojectsource.country", "earliest_date", "devstage_curation", "devstage_curation_coarse", "tissue_curation", "tissue_curation_coarse"], "primary_keys": ["rowid"], "primary_key_values": ["70277"], "units": {}, "query_ms": 8.177404997695703}