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Series GSE232850 Query DataSets for GSE232850
Status Public on Nov 24, 2023
Title ATM Loss and Therapeutic Vulnerabilities in Bladder Cancer
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary ATM plays a central role in the cellular response to DNA damage and ATM alterations are common in several tumor types including bladder cancer. However, the specific impact of ATM alterations on therapy response in bladder cancer is uncertain. Here, we combine preclinical modeling and clinical analyses to comprehensively define the impact of ATM alterations in bladder cancer. We show that ATM loss is sufficient to increase sensitivity to DNA damaging agents including cisplatin and radiation. Furthermore, ATM loss drives sensitivity to DNA repair targeted agents including PARP and ATR inhibitors. ATM loss alters the immune microenvironment and improves anti-PD1 response in preclinical bladder models but is not associated with improved anti-PD1/PD-L1 response in clinical cohorts. Finally, we show that ATM expression by IHC is strongly correlated with response to chemoradiotherapy. Together these data define a potential role for ATM as a predictive biomarker in bladder cancer.
 
Overall design RNA-seq of bladder tumors from BBN and BBN-ATM-KO tumor-bearing mice. When tumors reached 500 mm3 in size, mice were sacrificed and tumors harvested with half of the tumor snap-frozen for RNA sequencing (RNA-seq).
 
Contributor(s) Stawiski K, Zhou Y, Mouw K
Citation(s) 37992168
Submission date May 18, 2023
Last update date Nov 24, 2023
Contact name Konrad Stawiski
E-mail(s) konrad.stawiski@umed.lodz.pl
Phone 0048793264838
Organization name Medical University of Lodz
Department Department of Biostatistics and Translational Medicine
Street address Mazowiecka 15
City Lodz
ZIP/Postal code 91-215
Country Poland
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (10)
GSM7384545 BBN-ATM-WT tumor, sample 1
GSM7384546 BBN-ATM-WT tumor, sample 2
GSM7384547 BBN-ATM-WT tumor, sample 3
Relations
BioProject PRJNA974064

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Supplementary file Size Download File type/resource
GSE232850_normalized_counts.csv.gz 1.8 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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