Ontology highlight
ABSTRACT:
PROVIDER: PRJNA891663 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Genome-wide studies characterizing mutational landscape of bladder cancer revealed the exceptionally high rate of chromatin modifier genes in bladder cancer. Thus, epigenetic deregulation is a critical theme which needs further investigation for bladder cancer research. One of the highly mutated genes in bladder cancer is KDM6A, functioning as H3K27 demethylase and part of MLL3/4 complexes. To decipher the role of KDM6A in normal vs tumor setting, we identified the genomic localization profiles of KDM6A in normal, immortalized and cancer bladder cells. Our results showed differential occupancy of KDM6A at the genes involved in cell differentiation, chromatin organization and Notch signaling depending on the cell type and the mutation status of KDM6A. Transcription factor motif analysis revealed an enrichment for HES1 for the KDM6A peaks identified for T24 bladder cancer cell line, which has a truncating mutation in KDM6A and lacking demethylase domain and also for the other clusters showing KDM6A localization. For the first time, using co-immunoprecipitation experiments, we show that KDM6A is in complex with TLE co-repressors and HES1, and illustrate the potential interaction of KDM6A with TLE co-repressors, HES1, RUNX, HHEX transcription factors by computational structural biology models. Our work makes important contributions to the understanding of KDM6A malfunction in bladder cancer and provides models for the functioning of KDM6A independent of its demethylase activity.
2023-03-03 | GSE216625 | GEO
Project description:Acute Promyelocytic Leukemia (APL) is characterized by the t(15;17)(q22;q11.2) translocation, which creates a PML-RARA fusion gene that can initiate APL in mice. To discover cooperating mutations in this model, we sequenced a mouse APL genome to 15.6x haploid coverage, and discovered three somatic, non-synonymous mutations, of which one (Jak1 V657F) was recurrent. This mutation is identical to the JAK1 V658F mutation previously found in human APL and ALL samples. JAK1 V658F cooperates in vivo with PML-RARA, causing a rapidly fatal leukemia. We also discovered a somatic 150kb deletion involving the Kdm6a/Utx gene in the mouse APL genome; 3/14 additional mouse APL samples had similar deletions involving Kdm6a/Utx. Kdm6A/Utx, a histone H3K27 demethylase, was also deleted in 1/150 human AML samples tested. Whole genome sequencing of mouse cancer genomes provides an unbiased approach for discovering functionally relevant mutations that are also present in human leukemias. Spleens from Bl/6 Taconic mice were harvested and total RNA was extracted. A total of 15 specimens were analyzed using the Affymetrix Mouse Exon 1.0 ST platform.
2010-12-29 | E-GEOD-26128 | biostudies-arrayexpress
Project description:Transcription profiling by of rat bladder after inoculation with bladder cancer cells
2015-10-23 | E-MTAB-104 | ExpressionAtlas
Project description:Acute Promyelocytic Leukemia (APL) is characterized by the t(15;17)(q22;q11.2) translocation, which creates a PML-RARA fusion gene that can initiate APL in mice. To discover cooperating mutations in this model, we sequenced a mouse APL genome to 15.6x haploid coverage, and discovered three somatic, non-synonymous mutations, of which one (Jak1 V657F) was recurrent. This mutation is identical to the JAK1 V658F mutation previously found in human APL and ALL samples. JAK1 V658F cooperates in vivo with PML-RARA, causing a rapidly fatal leukemia. We also discovered a somatic 150kb deletion involving the Kdm6a/Utx gene in the mouse APL genome; 3/14 additional mouse APL samples had similar deletions involving Kdm6a/Utx. Kdm6A/Utx, a histone H3K27 demethylase, was also deleted in 1/150 human AML samples tested. Whole genome sequencing of mouse cancer genomes provides an unbiased approach for discovering functionally relevant mutations that are also present in human leukemias.
2010-12-30 | GSE26130 | GEO
Project description:Acute Promyelocytic Leukemia (APL) is characterized by the t(15;17)(q22;q11.2) translocation, which creates a PML-RARA fusion gene that can initiate APL in mice. To discover cooperating mutations in this model, we sequenced a mouse APL genome to 15.6x haploid coverage, and discovered three somatic, non-synonymous mutations, of which one (Jak1 V657F) was recurrent. This mutation is identical to the JAK1 V658F mutation previously found in human APL and ALL samples. JAK1 V658F cooperates in vivo with PML-RARA, causing a rapidly fatal leukemia. We also discovered a somatic 150kb deletion involving the Kdm6a/Utx gene in the mouse APL genome; 3/14 additional mouse APL samples had similar deletions involving Kdm6a/Utx. Kdm6A/Utx, a histone H3K27 demethylase, was also deleted in 1/150 human AML samples tested. Whole genome sequencing of mouse cancer genomes provides an unbiased approach for discovering functionally relevant mutations that are also present in human leukemias. DNA from 15 mouse APL tumors on the Bl/6 Taconic background (F10), DNA from one WT 129/SvJ mouse spleen, and pooled DNA derived from the spleens of 6-week-old, wild type, Bl/6 Taconic (parental strain) mice were analyzed using the Nimblegen Mouse CGH 3x720K WGT platform.
2010-12-30 | E-GEOD-26130 | biostudies-arrayexpress
Project description:Mouse Model of Clear Cell Sarcoma
2019-05-14 | E-GEOD-41293 | ExpressionAtlas
Project description:A genetic porcine model of cancer
2019-05-02 | E-MTAB-3382 | ExpressionAtlas
Project description:Purpose: The goals of this study are to compare 1. The transcription profile in KDM6A wildtype and KDM6A mutated urothelial bladder carcinoma. 2. The transcriptional changes in KDM6A mutated urothelial bladder carcinoma upon EZH2 inhibitor treatment.
2017-03-01 | GSE92723 | GEO
Project description:Transcription profiling of mouse Jardine SIDS Model
2015-10-22 | E-MEXP-2189 | ExpressionAtlas