Aim:

To investigate the existence of TMPRSS2:ERG fusion gene in circulating tumor cells (CTC) from prostate cancer patients and its potential in monitoring tumor metastasis.

Methods:

We analyzed the frequency of TMPRSS2: ERG and TMPRSS2:ETV1 transcripts in 27 prostate cancer biopsies from prostatectomies, and TMPRSS2:ERG transcripts in CTC isolated from 15 patients with advanced androgen independent disease using reverse transcription polymerase chain reaction (RT-PCR). Fluorescence in situ hybridization (FISH) was applied to analyze the genomic truncation of ERG, which is the result of TMPRSS2:ERG fusion in 10 of the 15 CTC samples.

Results:

TMPRSS2: ERG transcripts were found in 44% of our samples, but we did not detect expression of TMPRSS2:ETV1. Using FISH analysis we detected chromosomal rearrangements affecting the ERG gene in 6 of 10 CTC samples, including 1 case with associated TMPRSS2:ERG fusion at the primary site. However, TMPRSS2:ERG transcripts were not detected in any of the 15 CTC samples, including the 10 cases analyzed by FISH.

Conclusion:

Although further study is required to address the association between TMPRSS2:ERG fusion and prostate cancer metastasis, detection of genomic truncation of the ERG gene by FISH analysis could be useful for monitoring the appearance of CTC and the potential for prostate cancer metastasis.

References

1. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, et al. Cancer statistics, 2005. CA Cancer J Clin 2005; 55: 10–30. | PubMed | ISI |
2. Ulbright TM. Male genital tract. In: Alison MR, editor. The Cancer Handbook. London: Nature publishing group; 2002: p 665–87.
3. Xu XF, Zhou SW, Zhang X, Ye ZQ, Zhang JH, Ma X, et al. Prostate androgen-regulated gene: a novel potential target for androgen-independent prostate cancer therapy. Asian J Androl 2006; 8: 455–62. | Article | PubMed | ChemPort |
4. Yang J, Wu HF, Qian LX, Zhang W, Hua LX, Yu ML, et al. Increased expressions of vascular endothelial growth factor (VEGF), VEGF-C and VEGF receptor-3 in prostate cancer tissue are associated with tumor progression. Asian J Androl 2006; 8: 169–75. | Article | PubMed | ChemPort |
5. Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005; 310: 644–8. | Article | PubMed | ISI | ChemPort |
6. Tomlins SA, Mehra R, Rhodes DR, Smith LR, Roulston D, Helgeson BE, et al. TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer. Cancer Res 2006; 66: 3396–400. | Article | PubMed | ISI | ChemPort |
7. Yin JA, Grimwade D. Minimal residual disease evaluation in acute myeloid leukaemia. Lancet 2002; 360: 160–62. | Article | PubMed |
8. Rowley JD. Chromosome translocations: dangerous liaisons revisited. Nat Rev Cancer 2001; 1: 245–50. | Article | PubMed | ChemPort |
9. Winnes M, Lissbrant E, Damber JE, Stenman G. Molecular genetic analyses of the TMPRSS2–ERG and TMPRSS2–ETV1 gene fusions in 50 cases of prostate cancer. Oncol Rep 2007; 17: 1033–6. | PubMed | ISI | ChemPort |
10. Rajput AB, Miller MA, De Luca A, Boyd N, Leung S, Hurtado-Coll A, et al. Frequency of the TMPRSS2:ERG gene fusion is increased in moderate to poorly differentiated prostate cancers. J Clin Pathol 2007; 60: 1238–43. | Article | PubMed | ChemPort |
11. Nam RK, Sugar L, Wang Z, Yang W, Kitching R, Klotz LH, et al. Expression of TMPRSS2:ERG gene fusion in prostate cancer cells is an important prognostic factor for cancer progression. Cancer Biol Ther 2007; 6: 40–5. | Article | PubMed | ISI | ChemPort |
12. Mehra R, Tomlins SA, Shen R, Nadeem O, Wang L, Wei JT, et al. Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer. Mod Pathol 2007; 20: 538–44. | Article | PubMed | ChemPort |
13. Lapointe J, Kim YH, Miller MA, Li C, Kaygusuz G, van de Rijn M, et al. A variant TMPRSS2 isoform and ERG fusion product in prostate cancer with implications for molecular diagnosis. Mod Pathol 2007; 20: 467–73. | Article | PubMed | ChemPort |
14. Hermans KG, van Marion R, van Dekken H, Jenster G, van Weerden WM, Trapman J. TMPRSS2:ERG fusion by translocation or interstitial deletion is highly relevant in androgen-dependent prostate cancer, but is bypassed in late-stage an-drogen receptor-negative prostate cancer. Cancer Res 2006; 66: 10658–63. | Article | PubMed | ISI | ChemPort |
15. Demichelis F, Fall K, Perner S, Andren O, Schmidt F, Setlur SR, et al. TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene 2007; 26: 4596–9. | Article | PubMed | ChemPort |
16. Attard G, Clark J, Ambroisine L, Fisher G, Kovacs G, Flohr P, et al. Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer. Oncogene 2008; 27: 253–63. | Article | PubMed | ChemPort |
17. Perner S, Mosquera JM, Demichelis F, Hofer MD, Paris PL, Simko J, et al. TMPRSS2–ERG fusion prostate cancer: an early molecular event associated with invasion. Am J Surg Pathol 2007; 31: 882–8. | Article | PubMed | ISI |
18. Fleming JA, Stewart JW. A critical and comparative study of methods of isolating tumor cells from the blood. J Clin Pathol 1967; 20: 145–51. | Article | PubMed | ChemPort |
19. Pelkey TJ, Frierson HF Jr, Bruns DE. Molecular and immunological detection of circulating tumor cells and micrometastases from solid tumors. Clin Chem 1996; 42: 1369–81. | PubMed | ISI | ChemPort |
20. Smirnov DA, Zweitzig DR, Foulk BW, Miller MC, Doyle GV, Pienta KJ, et al. Global gene expression profiling of circulating tumor cells. Cancer Res 2005; 65: 4993–7. | Article | PubMed | ISI | ChemPort |
21. Ady N, Morat L, Fizazi K, Soria JC, Mathieu MC, Prapotnich D, et al. Detection of HER-2/neu-positive circulating epithelial cells in prostate cancer patients. Br J Cancer 2004; 90: 443–8. | Article | PubMed | ChemPort |
22. Li X, Wong C, Mysel R, Slobodov G, Metwalli A, Kruska J, et al. Screening and identification of differentially expressed transcripts in circulating cells of prostate cancer patients using suppression subtractive hybridization. Mol Cancer 2005; 4: 30. | Article | PubMed | ChemPort |
23. McIntyre IG, Spreckley K, Clarke RB, Anderson E, Clarke NW, George NJ. Optimization of the reverse transcriptase polymerase chain reaction for the detection of circulating prostate cells. Br J Cancer 2000; 83: 992–7. | Article | PubMed | ISI | ChemPort |
24. Llanes L, Ferruelo A, Paez A, Gomez JM, Moreno A, Berenguer A. The clinical utility of the prostate specific membrane antigen reverse-transcription/polymerase chain reaction to detect circulating prostate cells: an analysis in healthy men and women. BJU Int 2002; 89: 882–5. | Article | PubMed | ChemPort |
25. Llanes L, Paez A, Ferruelo A, Lujan M, Romero I, Berenguer A. Detecting circulating prostate cells in patients with clinically localized prostate cancer: clinical implications for molecular staging. BJU Int 2000; 86: 1023–7. | Article | PubMed | ChemPort |
26. Lu YJ, Birdsall S, Sum mersgill B, Smedley D, Osin P, Fisher C, et al. Dual colour fluorescence in situ hybridization to paraffin-embedded samples to deduce the presence of the der (X)t(X;18)(p11.2;q11.2) and involvement of either the SSX1 or SSX2 gene: a diagnostic and prognostic aid for synovial sarcoma. J Pathol 1999; 187: 490–6. | Article | PubMed | ISI | ChemPort |
27. Clark J, Merson S, Jhavar S, Flohr P, Edwards S, Foster CS, et al. Diversity of TMPRSS2–ERG fusion transcripts in the human prostate. Oncogene 2007; 26: 2667–73. | Article | PubMed | ISI | ChemPort |
28. Iljin K, Wolf M, Edgren H, Gupta S, Kilpinen S, Skotheim RI, et al. TMPRSS2 fusions with oncogenic ETS factors in prostate cancer involve unbalanced genomic rearrangements and are associated with HDAC1 and epigenetic reprogramming. Cancer Res 2006; 66: 10242–6. | Article | PubMed | ISI | ChemPort |
29. Wang J, Cai Y, Ren C, Ittmann M. Expression of Variant TMPRSS2/ERG Fusion Messenger RNAs Is Associated with Aggressive Prostate Cancer. Cancer Res 2006; 66: 8347–51. | Article | PubMed | ISI | ChemPort |
30. Soller MJ, Isaksson M, Elfving P, Soller W, Lundgren R, Panagopoulos I. Confirmation of the high frequency of the TMPRSS2/ERG fusion gene in prostate cancer. Genes Chromosomes Cancer 2006; 45: 717–9. | Article | PubMed | ISI | ChemPort |
31. Cerveira N, Ribeiro FR, Peixoto A, Costa V, Henrique R, Jeronimo C, et al. TMPRSS2-ERG gene fusion causing ERG overexpression precedes chromosome copy number changes in prostate carcinomas and paired HGPIN lesions. Neoplasia 2006; 8: 826–32. | Article | PubMed | ISI | ChemPort |
32. Yoshimoto M, Joshua AM, Chilton-Macneill S, Bayani J, Selvarajah S, Evans AJ, et al. Three-color FISH analysis of TMPRSS2/ERG fusions in prostate cancer indicates that genomic microdeletion of chromosome 21 is associated with rearrangement. Neoplasia 2006; 8: 465–9. | Article | PubMed | ISI | ChemPort |
33. Laxman B, Tomlins SA, Mehra R, Morris DS, Wang L, Helgeson BE, et al. Noninvasive detection of TMPRSS2:ERG fusion transcripts in the urine of men with prostate cancer. Neoplasia 2006; 8: 885–8. | Article | PubMed | ChemPort |
34. Perner S, Demichelis F, Beroukhim R, Schmidt FH, Mosquera JM, Setlur S, et al. TMPRSS2:ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer. Cancer Res 2006; 66: 8337–41. | Article | PubMed | ISI | ChemPort |
35. Hayes DF, Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Miller MC, et al. Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res 2006; 12: 4218–24. | Article | PubMed | ChemPort |
36. Lin B, Ferguson C, White JT, Wang S, Vessella R, True LD, et al. Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2. Cancer Res 1999; 59: 4180–4. | PubMed | ISI | ChemPort |

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.