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• W2109103692 abstract "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.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.The multitude of rare genomic and transcriptomic events detected in a high-risk tumor cohort offer novel opportunities for personalized oncology and their convergence on key pathways and functions has broad implications for precision medicine." @default.
• W2109103692 created "2016-06-24" @default.
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• W2109103692 date "2014-08-01" @default.
• W2109103692 modified "2023-10-12" @default.
• W2109103692 title "Heterogeneity in the inter-tumor transcriptome of high risk prostate cancer" @default.
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• W2109103692 doi "https://doi.org/10.1186/s13059-014-0426-y" @default.
• W2109103692 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4169643" @default.
• W2109103692 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25155515" @default.
• W2109103692 hasPublicationYear "2014" @default.
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