Fusion in the ETS gene family and prostate cancer.
It has recently been shown that the majority of prostate cancers harbour a chromosomal rearrangement that fuses the gene for an androgen-regulated prostate-specific serine protease, TMPRSS2, with a member of the ETS family of transcription factors, most commonly ERG. These are among the most common genetic alterations in any human solid tumour. This knowledge may provide us with clues to prostate carcinogenesis, and may lead to the development of important molecular-based biomarkers for patients with localised prostate cancer. The most common variant is fusion between the 5'-untranslated region of TMPRSS2 and the 3' region of ERG. However, over 20 other fusion variants have now been described (involving over 10 different genes) and the number of variants continues to grow. Fusion products can be identified by several techniques, including FISH, RT-PCR, and expression profiling using exon arrays. The protein products associated with the fusion transcripts have not been characterised, and the phenotypic expression of the various products of gene fusion on prostate cancer histology, or on the clinical course of cancer, are not yet understood. Several early cohort studies suggest that the presence of the TMPRSS2:ERG fusion product is associated with relatively poor cancer-specific survival. Studies that examine how individual variants and their associated phenotypes affect prostate cancer presentation and progression are required.
Narod
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SA
Department of Medicine, Womens College Research Institute, University of Toronto, ON, Canada. steven.narod@wchospital.ca
Seth
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Nam
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D006801:Humans; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*
D015514:Oncogene Proteins, Fusion; D050783:Proto-Oncogene Proteins c-ets; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human
Oncogene. 2007 Apr 19;26(18):2667-73
17043636
Mod Pathol. 2007 May;20(5):538-44
17334343
Cancer Res. 2007 Sep 1;67(17):7991-5
17804708
J Natl Cancer Inst. 2007 Oct 17;99(20):1525-33
17925536
Cancer Res. 2001 Feb 15;61(4):1686-92
11245484
Neoplasia. 2006 Jun;8(6):465-9
16820092
Br J Cancer. 2007 Dec 17;97(12):1690-5
17971772
Cancer Res. 2006 Nov 1;66(21):10242-6
17079440
Mod Pathol. 2007 Apr;20(4):467-73
17334351
Science. 2005 Oct 28;310(5748):644-8
16254181
Cancer Res. 2008 Jan 1;68(1):73-80
18172298
Genes Chromosomes Cancer. 2007 Nov;46(11):972-80
17654723
Cancer Res. 2006 Sep 1;66(17):8337-41
16951139
J Natl Cancer Inst. 2005 Jan 19;97(2):103-15
15657340
Oncogene. 2005 May 26;24(23):3847-52
15750627
Mod Pathol. 2007 Sep;20(9):921-8
17632455
Cancer Res. 2006 Sep 1;66(17):8347-51
16951141
Urology. 2007 Oct;70(4):630-3
17991527
Cancer Res. 2006 Apr 1;66(7):3396-400
16585160
Nat Genet. 2007 May;39(5):645-9
17401363
Cancer Biol Ther. 2007 Jan;6(1):40-5
17172822
Oncogene. 2007 Jul 5;26(31):4596-9
17237811
Cancer Res. 2006 Nov 15;66(22):10658-63
17108102
Clin Cancer Res. 2007 Sep 1;13(17):5103-8
17785564
Nature. 2007 Aug 2;448(7153):595-9
17671502
Eur J Cancer. 2005 Nov;41(16):2462-78
16213704
Genes Chromosomes Cancer. 2006 Jul;45(7):717-9
16575875
J Clin Pathol. 2007 Nov;60(11):1238-43
17259299
Mol Endocrinol. 2007 Aug;21(8):1835-46
17505060
Cancer Res. 2008 May 1;68(9):3094-8
18451133
Oncogene. 2008 Jan 10;27(3):253-63
17637754
Nat Genet. 2006 Jun;38(6):652-8
16682969
J Pathol. 2007 May;212(1):91-101
17385188