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Series GSE188739 Query DataSets for GSE188739
Status Public on Dec 02, 2021
Title Functional precision medicine pipeline combines comparative transcriptomics and tumor organoid modeling to identify be-spoke treatment strategies for glioblastoma
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome caused by germline mutations in TP53. TP53 is the most common mutated gene in human cancer occurring in 30-50% of glioblastomas (GBM). Here, we highlight a precision medicine platform to identify potential targets for a GBM patient with LFS. We used novel comparative transcriptomics analysis to identify genes that are uniquely overexpressed in a LFS GBM patient relative to a cancer compen-dium of 12,747 tumor RNA sequencing datasets including 200 GBMs. We then used ex vivo pa-tient derived organoid (PDO) viability assays with 4 patient derived cell lines to test efficacy of our identified target. Our comparative transcriptomics bioinformatics pipeline identified that STAT1 and STAT2 were significantly overexpressed in our patient indicating ruxolitinib, a Janus kinase 1 and 2 inhibitor, as a potential therapy. In our institutional high-grade glioma cohort of 45 patients, the LFS patient had the highest level of STAT1 and STAT2 expression. STAT1 and STAT2 expression levels in 4 cell lines derived from patients (including the LFS patient) corre-lated with levels identified in the respective parent tumors. Using 2D and 3D assays from pa-tient derived cells, our LFS patient of interest was among the most sensitive to ruxolitinib in comparison to patients with lower STAT1 and STAT2 expression levels. Additionally a sphe-roid-based drug screening assay (3D-PREDICT) was performed and used to identify further therapeutic targets. This manuscript supports the use of comparative transcriptomics to identify personalized therapeutic targets in a functional precision medicine platform for malignant brain tumors.
 
Overall design mRNA expression levels derived from RNA-seq for one patient tumor sample and four cell lines derived from patient tumors.
 
Contributor(s) Reed MR, Rodriguez A, Vaske OM
Citation(s) 34943910
Submission date Nov 12, 2021
Last update date Mar 04, 2022
Contact name Analiz Rodriguez
E-mail(s) ARodriguez@uams.edu
Organization name University of Arkansas for Medical Sciences
Department College of Medicine, Department of Neurosurgery
Lab Rodriguez Lab
Street address 4301 W. Markham St Slot 507
City Little Rock
State/province AR
ZIP/Postal code 72205
Country USA
 
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (5)
GSM5689101 Patient 1 tumor sample
GSM5689102 Patient 1 cell line sample
GSM5689103 Patient 17 cell line sample
Relations
BioProject PRJNA780017
SRA SRP345887

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE188739_RAW.tar 7.5 Mb (http)(custom) TAR (of RESULTS)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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