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| Status |
Public on Apr 07, 2021 |
| Title |
Temporal evolution of cellular heterogeneity during the progression to advanced, AR-negative prostate cancer [RRBS] |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
|
| Summary |
Despite advances in the development of highly effective androgen receptor (AR)-directed therapies for the treatment of men with advanced prostate cancer, acquired resistance ultimately ensues. A significant subset of patients with resistant disease develop AR-null, androgen-indifferent tumors that lose their luminal identify and display neuroendocrine features (neuroendocrine prostate cancer (NEPC)). Utilizing a genetically engineered mouse model, we have characterized the synergy between N-Myc overexpression and RB1 loss-of-function which results in the formation of AR-negative, poorly differentiated tumors with high metastatic potential. Single-cell-based approaches revealed striking changes to the transcriptome and chromatin accessibility during the transition to NEPC. Global DNA methylation and the N-Myc cistrome are redirected following RB1 loss. Altogether, our data provide new insight into the progression to NEPC.
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| |
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| Overall design |
RRBS in LNCaP human prostate cancer cells and mouse prostate tumors
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| |
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| Contributor(s) |
Brady NJ, Bagadion AM, Singh R, Rickman DS |
| Citation(s) |
34099734 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| P50 CA211024 |
Weill Cornell Medicine (WCM) SPORE in Prostate Cancer |
WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY |
Massimo Loda |
| R01 CA230913 |
Defining Molecular Determinants of Lineage Plasticity as a Mechanism of Treatment Resistance in Prostate Cancer |
WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY |
David S Rickman |
|
| |
| Submission date |
Jun 01, 2020 |
| Last update date |
Jun 09, 2021 |
| Contact name |
Nicholas Brady |
| E-mail(s) |
njb2003@med.cornell.edu
|
| Organization name |
Weill Cornell Medicine
|
| Department |
Pathology and Laboratory Medicine
|
| Street address |
1188 York Ave
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE151426 |
Temporal evolution of cellular heterogeneity during the progression to advanced, AR-negative prostate cancer |
|
| Relations |
| BioProject |
PRJNA636399 |
| SRA |
SRP265512 |
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