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Series GSE104986 Query DataSets for GSE104986
Status Public on Oct 03, 2018
Title KDM5B links cellular transcriptome heterogeneity to therapy resistance (RRBS)
Organism Homo sapiens
Experiment type Methylation profiling by high throughput sequencing
Summary The KDM5B histone H3 lysine 4 (H3K4) demethylase has been implicated in therapy resistance in multiple cancer types including breast cancer, but the underlying mechanism is poorly defined. Here we show that inhibition of KDM5B activity increases sensitivity to anti-estrogens by modulating estrogen-receptor (ER) signaling. Conversely, acquired resistance to KDM5 inhibitors leads to gain of ER chromatin binding and estrogen-independent growth. Sequencing of barcoded cell populations and mathematical modeling demonstrate selection for pre-existent genetically distinct endocrine-resistant cells, while resistance to KDM5 inhibitors is a switch to an acquired epigenetic state. Rare resistant cells can already be detected by single cell RNA-seq prior to treatment. Inhibition of KDM5B in luminal ER+ cells increases H3K4me3 broad domains at promoters and decreases cellular transcriptional heterogeneity. Higher transcriptome heterogeneity is associated with higher KDM5B levels and poor prognosis in ER+ luminal breast tumors.
 
Overall design Reduced representation bisulfite sequencing (RRBS) was performed on parental and multiple resistant breast cancer cell lines
 
Contributor(s) Hinohara K, Wu H, Michor F, Polyak K
Citation(s) 30472020
Submission date Oct 15, 2017
Last update date Jul 25, 2021
Contact name Kornelia Polyak
E-mail(s) kornelia_polyak@dfci.harvard.edu
Phone 617-632-2106
Organization name Dana-Farber Cancer Institute
Department Medical Oncology
Lab Polyak
Street address 450 Brookline Ave
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (10)
GSM2813210 C49R_1 (RRBS)
GSM2813211 C49R_2 (RRBS)
GSM2813212 C70R_1 (RRBS)
This SubSeries is part of SuperSeries:
GSE104988 KDM5B links cellular transcriptome heterogeneity to therapy resistance
Relations
BioProject PRJNA414334
SRA SRP119971

Download family Format
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Supplementary file Size Download File type/resource
GSE104986_RAW.tar 132.2 Mb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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