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Series GSE152667 Query DataSets for GSE152667
Status Public on Jun 18, 2020
Title CARM1 inhibition reduces histone acetyltransferase activity causing synthetic lethality in CREBBP/EP300 mutated lymphomas [RNA-seq_Toledo]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Somatic mutations affecting CREBBP and EP300 are a hallmark of Diffuse Large B Cell Lymphoma (DLBCL). These mutations are frequently monoallelic, within the histone acetyltransferase (HAT) domain and usually mutually exclusive, suggesting that they might affect a common pathway and their residual WT expression is required for cell survival. Using in vitro and in vivo models, we found that inhibition of CARM1 activity (CARM1i) slows DLBCL growth and that the levels of sensitivity are positively correlated with the CREBBP/EP300 mutation load. Conversely, treatment of DLBCLs that do not have CREBBP/EP300 mutations with CARM1i and a CBP/p300 inhibitor revealed a strong synergistic effect. Our mechanistic data show that CARM1i further reduces the HAT activity of CBP genome wide and downregulates CBP target genes in DLBCL cells, resulting in a synthetic lethality that leverages the mutational status of CREBBP/EP300 as a biomarker for the use of small molecule inhibitors of CARM1 in DLBCL and other cancers.
 
Overall design 6 samples - 3 replicates DMSO-treated, 3 replicates CARM1i treated
 
Contributor(s) Veazey KJ, Cheng D, Lin K, Villarreal OD, Gao G, Perez-Oquendo M, Van HT, Stratton SA, Green M, Xu H, Lu Y, Bedford MT, Santos MA
Citation(s) 32576962
Submission date Jun 17, 2020
Last update date Sep 17, 2020
Contact name Margarida Almeida Santos
Organization name UT MD Anderson Cancer Center
Department Epigenetics and Molecular Carcinogenesis
Lab Santos Lab
Street address 1515 Holcombe Blvd Mail code 1000
City Houston
State/province Texas
ZIP/Postal code 77030
Country USA
 
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (6)
GSM4623093 Toledo_CARM1i_1
GSM4623094 Toledo_CARM1i_2
GSM4623095 Toledo_CARM1i_3
This SubSeries is part of SuperSeries:
GSE152668 CARM1 inhibition reduces histone acetyltransferase activity causing synthetic lethality in CREBBP/EP300 mutated lymphomas
Relations
BioProject PRJNA640010
SRA SRP267643

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
GSE152667_Toledo_DESeq_counts.txt.gz 763.7 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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