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| Status |
Public on Jul 21, 2014 |
| Title |
Heterogeneity in the inter-tumor transcriptome of high risk prostate cancer |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by array
Genome variation profiling by genome tiling array
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| Summary |
Background: Genomic analyses of hundreds of prostate tumors have defined a diverse landscape of mutations and genome rearrangements, but the transcriptomic effect of this complexity is less well understood, particularly at the individual tumor level. We selected a cohort of 25 high-risk prostate tumors, representing the lethal phenotype, and applied deep RNA-sequencing and matched whole genome sequencing, followed by detailed molecular characterization.
Results: Ten tumors were exposed to neo-adjuvant hormone therapy and expressed marked evidence of therapy response in all except one extreme case, which demonstrated early resistance via apparent neuroendocrine transdifferentiation. We observe high inter-tumor heterogeneity, including unique sets of outlier transcripts in each tumor. Interestingly, outlier expression converged on druggable cellular pathways associated with cell cycle progression, translational control or immune regulation, suggesting distinct contemporary pathway affinity and a mechanism of tumor stratification. We characterize hundreds of novel fusion transcripts, including a high frequency of ETS fusions associated with complex genome rearrangements and the disruption of tumor suppressors. Remarkably, several tumors express unique but potentially-oncogenic non-ETS fusions, which may contribute to the phenotype of individual tumors, and have significance for disease progression. Finally, one ETS-negative tumor has a striking tandem duplication genotype which appears to be highly aggressive and present at low recurrence in ETS-negative prostate cancer, suggestive of a novel molecular subtype.
Conclusions: The multitude of rare genomic and transcriptomic events detected in a high-risk tumors cohort offer novel opportunities for personalized oncology and their convergence on key pathways and functions has broad implications for precision medicine.
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| Overall design |
28 samples were analyzed, no replicates, using Agilent aCGH arrayscompetitively hybridized against a male reference pool
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| Contributor(s) |
Wyatt AW, Collins CC |
| Citation(s) |
25155515 |
| Submission date |
Feb 13, 2014 |
| Last update date |
Oct 20, 2014 |
| Contact name |
Shawn Anderson |
| E-mail(s) |
Sanderson@prostatecentre.com
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| Organization name |
Vancouver Prostate Centre
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| Lab |
Laboratory for Advanced Genome Analysis
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| Street address |
2660 Oak Street
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| City |
Vancouver |
| State/province |
BC |
| ZIP/Postal code |
V6H3Z6 |
| Country |
Canada |
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| Platforms (2) |
| GPL10123 |
Agilent-022060 SurePrint G3 Human CGH Microarray 4x180K (Feature Number version) |
| GPL10152 |
Agilent-021924 SurePrint G3 Human CGH Microarray 8x60K (Feature Number version) |
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| Samples (28)
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| Relations |
| BioProject |
PRJNA238250 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE55016_RAW.tar |
255.8 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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