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| Status |
Public on Jul 14, 2021 |
| Title |
RNA splicing factors SRRM3 and SRRM4 distinguish molecular phenotypes of castration-resistant neuroendocrine prostate cancer [methylation] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
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| Summary |
Neuroendocrine (NE) differentiation in metastatic castration-resistant prostate cancer (mCRPC) usually develops through cellular plasticity. We recently characterized two mCRPC phenotypes with NE features; Androgen receptor (AR)-positive, NE-positive amphicrine prostate cancer (AMPC) and AR-negative small cell or neuroendocrine prostate cancer (SCNPC). Here, we interrogate the RE-1 silencing transcription factor (REST) pathway in mCRPC and demonstrate that SRRM3 has analogous functions to SRRM4 and mediates NE differentiation through alternative splicing of REST. We scrutinize transcriptome datasets across species and tumor types and discover that SRRM3 and SRRM4 expression define molecular phenotypes in AMPC and SCNPC. Notably, we characterize two AMPC phenotypes driven by either REST attenuation or ASCL1 activity and three SCNPC phenotypes with progressive activation of neuronal transcription factor programs. Together, our data provides a biological framework for classifying NE phenotypes in mCRPC that could be useful for future therapeutic development and precision medicine applications.
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| Overall design |
Transcriptome profiling of human prostate tumor cell lines using Illumina TruSeq Library prep sequenced on Illumina NovaSeq and methylation profiling using Illumina Infinium MethylationEPIC BeadChip arrays.
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| Contributor(s) |
Labrecque MP, Brown LG, Coleman IM, Lakely B, Brady NJ, Lee JK, Nguyen HM, Li D, Hanratty B, Haffner MC, Rickman DS, True LD, Lin DW, Lam H, Alumkal JJ, Corey E, Nelson PS, Morrissey C |
| Citation(s) |
34312180 |
| Submission date |
Sep 25, 2020 |
| Last update date |
Jul 28, 2021 |
| Contact name |
Ilsa Coleman |
| E-mail(s) |
icoleman@fredhutch.org
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| Phone |
206-667-1703
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| Organization name |
Fred Hutchinson Cancer Center
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| Department |
Human Biology
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| Lab |
Peter Nelson
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| Street address |
1100 Fairview Ave N, E2-112
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98109 |
| Country |
USA |
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| Platforms (1) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE158599 |
RNA splicing factors SRRM3 and SRRM4 distinguish molecular phenotypes of castration-resistant neuroendocrine prostate cancer |
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| Relations |
| BioProject |
PRJNA665739 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE158598_RAW.tar |
193.1 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
| Processed data are available on Series record |
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