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Title: Identification of novel oncogenic events occurring early in prostate carcinogenesis using purified autologous malignant and non-malignant prostate epithelial cells.
Austin Authors: Sluka, Pavel;Pezaro, Carmel;Wardan, Hady;Sengupta, Shomik ;Davis, Ian D
Affiliation: Eastern Health Clinical School, Faculty of Medicine, Nursing& Health Sciences, Monash University, Melbourne, Australia
Department of Surgery, University of Melbourne, Melbourne, Australia
Department of Urology, Austin Health, Heidelberg, Victoria, Australia
Eastern Health, Melbourne, Australia
Issue Date: May-2019
Date: 2019-02-03
Publication information: BJU International 2019; 123(Suppl 5): 27-35
Abstract: To interrogate enriched prostate cancer cells and autologous non-malignant prostate epithelial cells from men with localized prostate cancer, in order to identify early oncogenic pathways. Previous work characterizing early oncogenic changes in prostate cancer, including that of the Cancer Genome Atlas, has used tissue containing cells from non-malignant components as well as from non-epithelial tissue compartments, diluting cancer-related changes. We collected malignant and matched nonmalignant prostatectomy samples from men with adenocarcinoma involving two or more contiguous areas in only one lobe of the prostate. Tissue samples from both lobes were subjected to digestion and single-cell suspensions were prepared. EpCAM positive cells from cancerous and contralateral non-malignant (control) samples were isolated using magnetic beads, ensuring uniform populations were obtained for each donor. Unbiased RNA-Seq was used to measure gene expression and for detection of transcribed mutations or splice variants that were over- or under-represented in malignant prostate epithelial cells relative to autologous control prostate epithelial cells. From five patient samples we identified 17 genes that were altered in prostate cancer epithelial cells, with 82% of genes being downregulated. Three genes, TDRD1, ANGTL4, and CLDN3, were consistently upregulated in malignant tissue. Malignant cells from three of the five patients showed evidence of upregulated ERG signaling, however only one of these contained a TMPRSS2-ERG rearrangement. We did not identify mutations, gene rearrangements, or splice variants that were consistent amongst the patients. Events occurring early in prostate cancer oncogenesis in these samples were characterized by a predominant downregulation of gene expression along with upregulation of TDRD1, ANGTL4, and CLDN3. No consistent mutations or splice variants were observed, however upregulation of ERG signaling was seen both in the presence and absence of the classic TMPRSS2-ERG rearrangement. This article is protected by copyright. All rights reserved.
DOI: 10.1111/bju.14695
ORCID: 0000-0003-3357-1216
Journal: BJU International
PubMed URL: 30712320
Type: Journal Article
Appears in Collections:Journal articles

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