GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE55016 Query DataSets for GSE55016
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
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.

Overall design 28 samples were analyzed, no replicates, using Agilent aCGH arrayscompetitively hybridized against a male reference pool
Contributor(s) Wyatt AW, Collins CC
Citation(s) 25155515
Submission date Feb 13, 2014
Last update date Oct 20, 2014
Contact name Shawn Anderson
Organization name Vancouver Prostate Centre
Lab Laboratory for Advanced Genome Analysis
Street address 2660 Oak Street
City Vancouver
State/province BC
ZIP/Postal code V6H3Z6
Country Canada
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)
Samples (28)
GSM1327943 T21_1007RT
GSM1327944 T23_1015LP
GSM1327945 T1_274LP
BioProject PRJNA238250

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE55016_RAW.tar 255.8 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap