Monoallelic expression of TMPRSS2/ERG in prostate cancer stem cells

Euan S. Polson, John L. Lewis, Hamza Celik, Vincent M. Mann, Michael J. Stower, Matthew S. Simms, Greta Rodrigues, Anne T. Collins and Norman J. Maitland ()
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Euan S. Polson: YCR Cancer Research Unit, University of York
John L. Lewis: YCR Cancer Research Unit, University of York
Hamza Celik: Laboratoire de Chimie Bactérienne, UMR7283-CNRS, Aix-Marseille Université
Vincent M. Mann: Hull York Medical School, University of Hull
Michael J. Stower: York District Hospital
Matthew S. Simms: Hull York Medical School, University of Hull
Greta Rodrigues: Hull Royal Infirmary
Anne T. Collins: YCR Cancer Research Unit, University of York
Norman J. Maitland: YCR Cancer Research Unit, University of York

Nature Communications, 2013, vol. 4, issue 1, 1-9

Abstract: Abstract While chromosomal translocations have a fundamental role in the development of several human leukaemias, their role in solid tumour development has been somewhat more controversial. Recently, it was shown that up to 80% of prostate tumours harbour at least one such gene fusion, and that the most common fusion event, between the prostate-specific TMPRSS2 gene and the ERG oncogene, is a critical, and probably early factor in prostate cancer development. Here we demonstrate the presence and expression of this significant chromosomal rearrangement in prostate cancer stem cells. Moreover, we show that in the prostate epithelial hierarchy from both normal and tumour tissues, TMPRSS2 transcription is subjected to tight monoallelic regulation, which is retained upon asymmetric division and relaxed during epithelial cell differentiation. The presence and expression of TMPRSS2/ERG in prostate stem cells would provide ERG-driven survival advantages, allowing maintenance of this mutated genotype.

Date: 2013
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DOI: 10.1038/ncomms2627

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