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; Norman J Maitland

doi:10.1038/ncomms2627

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, Norman J Maitland

Cancer Research Unit

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	1623
Pages (from-to)	1-9
Journal	Nature Communications
Volume	4
DOIs	https://doi.org/10.1038/ncomms2627
Publication status	Published - 27 Mar 2013

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http://www.nature.com/ncomms/journal/v4/n3/full/ncomms2627.html

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title = "Monoallelic expression of TMPRSS2/ERG in prostate cancer stem cells",

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.",

author = "Polson, {Euan S} and Lewis, {John L} and Hamza Celik and Mann, {Vincent M} and Stower, {Michael J} and Simms, {Matthew S} and Greta Rodrigues and Collins, {Anne T} and Maitland, {Norman J}",

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T1 - Monoallelic expression of TMPRSS2/ERG in prostate cancer stem cells

AU - Polson, Euan S

AU - Lewis, John L

AU - Celik, Hamza

AU - Mann, Vincent M

AU - Stower, Michael J

AU - Simms, Matthew S

AU - Rodrigues, Greta

AU - Collins, Anne T

AU - Maitland, Norman J

PY - 2013/3/27

Y1 - 2013/3/27

N2 - 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.

AB - 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.

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JO - Nature Communications

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Monoallelic expression of TMPRSS2/ERG in prostate cancer stem cells

Abstract

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