In situ sequencing identifies TMPRSS2–ERG fusion transcripts, somatic point mutations and gene expression levels in prostate cancers. Issue 2 (4th August 2014)

• Record Type: Journal Article
• Authors: Kiflemariam, Sara; Mignardi, Marco; Ali, Muhammad Akhtar; Bergh, Anders; Nilsson, Mats; Sjöblom, Tobias
• Is Part Of: Journal of pathology. Volume 234:Issue 2(2014)
• Page Start: 253
• Page End: 261
• Publication Date: 2014-08-04
• Subjects: Pathology -- Periodicals; 616.07
• DOI: 10.1002/path.4392
• Languages: English
• ISSNs: 0022-3417

Abstract

<abstract abstract-type="main" id="path4392-abs-0001"> <title>Abstract</title> <p id="path4392-para-0001">Translocations contribute to the genesis and progression of epithelial tumours and in particular to prostate cancer development. To better understand the contribution of fusion transcripts and visualize the clonal composition of multifocal tumours, we have developed a technology for multiplex <italic>in situ</italic> detection and identification of expressed fusion transcripts. When compared to immunohistochemistry, <italic>TMPRSS2–ERG</italic> fusion‐negative and fusion‐positive prostate tumours were correctly classified. The most prevalent <italic>TMPRSS2–ERG</italic> fusion variants were visualized, identified, and quantitated in human prostate cancer tissues, and the ratio of the variant fusion transcripts could for the first time be directly determined by <italic>in situ</italic> sequencing. Further, we demonstrate concurrent <italic>in situ</italic> detection of gene expression, point mutations, and gene fusions of the prostate cancer relevant targets <italic>AMACR</italic>, <italic>AR</italic>, <italic>TP53</italic>, and <italic>TMPRSS2–ERG</italic>. This unified approach to <italic>in situ</italic> analyses of somatic mutations can empower studies of intra‐tumoural heterogeneity and future tissue‐based diagnostics of mutations and translocations. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd</p> </abstract>