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Series GSE116170 Query DataSets for GSE116170
Status Public on Jul 11, 2018
Title Transcriptional properties of estrogen receptor fusion genes.
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary RNA sequencing (RNA-seq) detects estrogen receptor alpha gene (ESR1) fusion transcripts in estrogen receptor positive (ER+) breast cancer but their role in disease pathogenesis remains unclear. Herein we examined multiple in-frame and out-of-frame ESR1 fusions and found that two, both identified in advanced endocrine treatment resistant disease, encoded stable and functional in-frame fusion proteins. In both examples, ESR1-e6>YAP1 and ESR1-e6>PCDH11X, the N-terminal, DNA binding and dimerization motifs encoded by exons 2-6 were fused to C terminal sequences from the partner gene. Functional properties included estrogen-independent growth, constitutive expression of ER target genes, anti-estrogen resistance, induction of cellular motility in vitro and the development of lung metastasis in vivo. Chromatin immunoprecipitation and RNA sequencing experiments showed both fusions uniquely activated a metastasis-associated transcriptional program. ESR1-e6>YAP1 and ESR1-e6>PCDH11X-induced growth remained sensitive to a CDK4/6 inhibitor, palbociclib, and a patient-derived xenograft (PDX) naturally expressing the ESR1-e6>YAP1 fusion was also responsive. Transcriptionally active ESR1 fusions therefore trigger both endocrine therapy resistance and metastatic progression explaining the association with fatal disease progression, although CDK4/6 inhibitor treatment is predicted to be effective.
 
Overall design HA-ChIP-seq and RNA-seq of stable T47D breast cancer cell lines expressing HA-tagged ESR1 constructs in hormone deprived media -/+ E2. HA-ChIP DNA from YFP-HA expressing cells was used as input.
 
Contributor(s) Ellis MJ, Lei JT
Citation(s) 30089255
Submission date Jun 22, 2018
Last update date Mar 27, 2019
Contact name Jonathan Thomas Lei
E-mail(s) jlei@bcm.edu
Organization name Baylor College of Medicine
Department Medicine - Lester and Sue Smith Breast Center
Lab Matthew Ellis Lab
Street address 1 Baylor Plaza
City Houston
State/province TX
ZIP/Postal code 77030
Country USA
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (15)
GSM3212399 T47D_ESR1WT_noE2_HA_ChIPseq
GSM3212400 T47D_ESR1YAP1_noE2_HA_ChIPseq
GSM3212401 T47D_ESR1PCDH11X_noE2_HA_ChIPseq
Relations
BioProject PRJNA477539
SRA SRP151140

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Supplementary file Size Download File type/resource
GSE116170_RAW.tar 22.1 Mb (http)(custom) TAR (of BED, TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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