Hormone-sensitive prostate cancer: a case of ETS gene fusion heterogeneity
- G Attard1,2,
- C Jameson1,
- J Moreira1,2,
- P Flohr2,
- C Parker1,2,
- D Dearnaley1,2,
- C S Cooper2,
- J S de Bono1,2
- Dr J S de Bono, Senior Lecturer and Consultant Medical Oncologist, Cancer Research UK Centre for Cancer Therapeutics, The Institute for Cancer Research, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, UK; jdebono{at}icr.ac.uk
- Accepted 17 November 2008
- Published Online First 9 December 2008
Abstract
Fusion of the hormone-regulated gene TMPRSS2 with ERG occurs in 50–70% of prostate cancers; fusions of ETV1 with one of several partners occur in approximately 10% of prostate cancers. These two translocations are mutually exclusive. The presence of subclasses of these chromosomal rearrangements may indicate worse prognosis, with the subclass 2+Edel, which has duplication of TMPRSS2:ERG fusion sequences, indicating particularly poor survival. However as this case shows, significant heterogeneity can exist with ERG and ETV1 rearrangements occurring in both prostate intra-epithelial neoplasia and cancer in the same prostatectomy specimen and with adjacent cancer areas containing a single copy, duplication and even triplication of the rearranged locus. As the majority of ETS gene fusions are hormone regulated, they could explain the pathogenesis underlying exquisitely hormone-sensitive prostate cancer. This is exemplified by the case presented here of a patient diagnosed in 1991 who remains asymptomatic and chemotherapy-naïve after having long-lasting tumour responses to multiple lines of systemic hormonal treatments.
Footnotes
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Funding: GA, JM and JSDeB are employed by the Section of Medicine of the Institute of Cancer Research that is supported by a Cancer Research UK programme grant and an Experimental Cancer Medical Centre (ECMC) grant from Cancer Research UK and the Department of Health (Ref: C51/A7401). GA was also supported by the Royal Marsden Hospital General Research Council Fund. CP was supported by Cancer Research UK. CSC was supported by the Grand Charity of Freemasons. CSC, PF and CP were also supported by the National Cancer Research Institute Prostate Cancer Collaborative. PF was also supported by the Prostate Cancer Charity.
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Competing interests: None.
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Ethics approval: Obtained.
