{"database": "metadata", "table": "run_metadata", "rows": [[53577, "SRR9944753", "SRX6693252", "SRS5250592", "SRP218009", "PRJNA559652", "Aberrant AKT Activation Drives Ganglioneuroma and Can Be Therapeutically Targeted by mTOR Inhibitors", "GSE135682", "Transcriptome Analysis", "Peripheral sympathetic nervous system tumors are the most common extra cranial pediatric tumors in children and include neuroblastoma  ganglioneuroma and intermixed ganglioneuroblastoma. Ganglioneuroma can be induced by activating mutations of the RET proto oncogene or activated Ras in murine models  but the etiology and molecular pathogenesis of this disease is unknown for the majority of human ganglioneuromas. Surgery is the only effective therapy for ganglioneuroma which can be challenging due to tumor location and compression of surrounding structures. Thus  there is great potential benefit to the definition of presurgical therapies that can reduce the size and extent of these tumors  and therefore limit morbidity. We found high levels of phosphorylated AKT in most of human ganglioneuromas  but only in a small portion of human poorly differentiated neuroblastomas p<0.0001  Fisher's exact test. As a result  we created zebrafish transgenic for constitutively activated myr Akt2 in the sympathetic nervous system. These zebrafish were found to develop benign ganglioneuroma without xxx to neuroblastoma. Zebrafish tumors displayed high expression of phosphorylated Akt and the downstream Akt targets  phosphorylated mTOR  S6 and EIF4EBP1. Histopathological and comparative genomic analyses revealed that zebrafish ganglioneuroma highly resembles human ganglioneuroma. Inhibition of the downstream AKT target  mTOR  using clinically available inhibitors effectively reduced tumor burden in zebrafish embryos transplanted with primary ganglioneuroma. Our results implicate activated and phosphorylated AKT as a tumorigenic driver in ganglioneuroma  and propose inhibition of the AKT target kinase mTOR as an ideal candidate to treat patients with ganglioneuroma. Overall design: RNA Seq for zebrafish tumor cells from MYCN and myrAKT transgenic fish", null, "pubmed:32728700", null, "MYCN#1", "GSM4026000", null, "tissue:Zebrafish neuroblastoma tumor cells|genotype/variation:MYCN transgenic fish|cell type:neuroblastoma cells", "MYCN#1", "post acquiring the raw fastq format paired end RNA seq reads  we inspected the sequencing quality using fastqc v0.11.5  and removed standard Illumina adapters from the 3\u2019 end using Trim Galore v0.4.4. The processed reads were then aligned to the GRCz10 version of the zebrafish reference genome using Tophat v2.1.1. The GTF format UCSC gene models  obtained from the iGenomes website  was provided as an annotation reference  G option of Tophat. post the alignment  the BAM format files were sorted by reads name using Samtools v1.5  and the reads mapped to each gene were counted using HTSeq count v0.6.1. edgeR library was applied to normalize read counts across samples and identify genes that are differentially expressed between conditions in R. Genome build: GRCz10 Supplementary files format and content: counts", "Zebrafish neuroblastoma tumor cells", "None", "EGFP+ or mCherry+ tumor cells were sorted  then total RNA was extracted with Trizol LS. Total RNA was depleted of ribosomal RNA with the SMARTer Universal Low Input RNA Kit Clontech. Enriched mRNA was then applied to library preparation according to manufacturer\u2019s protocol NEBNext Ultra. post repeated quality control for average DNA input size of 300 bp  the samples were sequenced on aIllumina NextSeq 500 with 2X75bp paired end reads.", "EGFP+ neuroblastoma cells or mCherry+ ganglioneuroma cells were harvested from tumor bearing MYCN or myrAkt transgenic zebrafish. Tumors were mechanically homogenized and EGFP+ or mCherry+ cells were sorted directly into Trizol LS", "genotype/variation:MYCN transgenic fish|cell type:neuroblastoma cells", "GSM4026000", "GSM4026000: MYCN#1; Danio rerio; RNA Seq", "GSM4026000", null, "1", "EGFP+ or mCherry+ tumor cells were sorted  then total RNA was extracted with Trizol LS. Total RNA was depleted of ribosomal RNA with the SMARTer Universal Low Input RNA Kit Clontech. Enriched mRNA was then applied to library preparation according to manufacturer's protocol NEBNext Ultra. post repeated quality control for average DNA input size of 300 bp  the samples were sequenced on aIllumina NextSeq 500 with 2X75bp paired end reads.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "ILLUMINA", "NextSeq 500", null, "SRP218009", null, null, "MYCN_1_R1_001.fastq.gz MYCN_1_R2_001.fastq.gz", "fastq fastq", 12249512250.0, 81663415.0, "GSM4026000 r1", "0:75 1:75", "A:3146759551;C:2963459721;G:3078804965;T:3060035031;N:452982", 75, 75, null, null, 3146759551, 2963459721, 3078804965, 3060035031, 452982, "SRX6693252", "SRS5250592", "SRA937501", "GEO", "Thomas Look, Pediatric Oncology, Dana-Farber Cancer Institute", 2, 0.95937, 0.95322, 0.06466, 0.06119, 0.7484, 0.76071, 0.51653, 0.51684, 75, 75, "B", "B", "biological fallback assumption", "illumina", "nextseq", "full_length", "rrna_depletion", "nebnext", "bulk", "unknown", "unknown", null, "United States", "2019-08-10", "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": ["53577"], "units": {}, "query_ms": 9.238929000275675}