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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
32142 SRR29068708 SRX24593111 SRS21331201 SRP508364 PRJNA1112809 tp53 R217H and R242H Mutant Zebrafish Display Dysfunctional p53 Hallmarks and Recapitulate LFS Phenotypes [RNA seq] GSE267760 Transcriptome Analysis Li Fraumeni syndrome LFS is a hereditary cancer predisposition syndrome associated with a highly penetrant and diverse tumor spectrum characterized by germline mutations in the TP53 tumor suppressor gene. To better understand how TP53 mutations predispose individuals with LFS to cancer development we characterized tp53 R217H and R242H zebrafish lines as the first zebrafish p53 hotspot mutants human R248 and R273H. These mutants have lost several key wildtype p53 functions and recapitulate many LFS phenotypes. Specifically we have shown that the R217H and R242H alleles result in partial to no activation of key p53 target genes are resistant to apoptosis in a dominant negative manner and exhibit a defective G1 cell cycle checkpoint in vivo. The loss of these wildtype p53 functions predisposed the fish to develop spontaneous tumors as early as 6 month of age. Tumor histology resembles human sarcomas a predominant LFS tumor type. tp53 R242H mutants developed tumors earlier with a higher lifetime incidence than tp53 null or R217H mutants suggesting it is a more aggressive mutation while the R217H allele may be hypomorphic. Additionally we observed mutation specific differences both in the tumor type and sex bias across tp53 null R217H and R242H genotypes with associated diverse transcriptomic and DNA methylome profiles impacting metabolism cell signalling and biological macromolecule synthesis and degradation. These tp53 zebrafish mutants demonstrate fidelity to their human counterparts and provide new insights into underlying tumorigenesis mechanisms and kinetics which may inform more tailored tumor surveillance approaches and novel therapeutic targets in LFS. Overall design: We generated tp53 zebrafish mutants representing two of the most common mutation residues found in human cancers tp53 R217H and R242H human R248 and R273 using CRISPR to knock in the mutations and also obtained a CG1 tp53 null line from the Langenau lab Ignatius et al. 2018. We also used the transparent casper strain as a comparison to zebrafish with wildtype p53. Of note the tp53 null fish are in the CG1 background while the casper tp53 R217H and tp53 R242H fish are in the AB background. We performed bulk RNA sequencing on homozygous pooled samples with fifty 30 hpf larvae exposed to 0 or 30 Gy of irradiation at xxx hpf. We had three biological replicate for each genotype and treatment group for a total of 8 different groups with 24 samples total casper 0 Gy casper 30 Gy tp53 null 0 Gy tp53 null 30 Gy tp53 R217H 0 Gy tp53 R217H 30 Gy tp53 R242H 0 Gy tp53 R242H 30 Gy.       tp53 R242H/R242H 30 Gy biol rep 2 GSM8275257   source name:whole embryo|tissue:whole embryo|Stage:30 hpf|strain:AB|genotype:tp53 R242H/R242H|treatment:30 Gy|geo loc name:missing|collection date:missing tp53 R242H/R242H 30 Gy biol rep 2 The RNA Seq data were mapped with STAR v2.7 to generate BAM files and transcripts were quantified with RSEM using the zebrafish V4.3.2 transcript annotation. Assembly: GRCz11 Supplementary files format and content: tab delinated text file includes count matrix with each sample whole embryo Larvae were exposed to either 0 or 30 Gy of irradiation at xxx hpf. Each RNA sample was extracted from 50 zebrafish embryos anesthetized with tricaine MS 222 and homogenized in 500μL TRIzol reagent Life Technologies 15596026 using a 1mL syringe and 23G needle. Lysed samples were purified and DNAse treated using the Direct zol RNA MicroPrep kit Zymo Research Corperation R2060. 4ug of total RNA from each sample were sent for RNA sequencing. RNA Libraries were constructed for standard paired read RNA sequencing by GeneWiz. Larvae were maintained at 28C and samples were collected at 30 hpf. tissue:whole embryo|Stage:30 hpf|strain:AB|genotype:tp53 R242H/R242H|treatment:30 Gy GSM8275257 GSM8275257: tp53 R242H/R242H 30 Gy biol rep 2; Danio rerio; RNA Seq GSM8275257 r1 GSM8275257 1 Each RNA sample was extracted from 50 zebrafish embryos anesthetized with tricaine MS 222 and homogenized in 500μL TRIzol reagent Life Technologies 15596026 using a 1mL syringe and 23G needle. Lysed samples were purified and DNAse treated using the Direct zol RNA MicroPrep kit Zymo Research Corperation R2060. 4ug of total RNA from each sample were sent for RNA sequencing. RNA Libraries were constructed for standard paired read RNA sequencing by GeneWiz.   RNA-Seq TRANSCRIPTOMIC cDNA PAIRED ILLUMINA Illumina NovaSeq 6000   SRP508364   loader:fastq load.py 242I-2_R1_001.fastq.gz 242I-2_R2_001.fastq.gz fastq fastq 14876409900.0 49588033.0 GSM8275257 r1 0:150 1:150 A:4155568434;C:3275443734;G:3414514883;T:4028089617;N:2793232 150 150     4155568434 3275443734 3414514883 4028089617 2793232 SRX24593111 SRS21331201     Berman Lab, Children's Hospital of Eastern Ontario Research Institute                       B B biological fallback assumption illumina novaseq_era unknown cdna_unspecified unknown bulk bulk bulk   Canada 2024-05-17 Pharyngula Embryo Whole Organism All anatomical structures