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Overexpression of C-MYC oncogene in prostate cancer predicts biochemical recurrence

Abstract

Alterations of chromosome 8, including amplification at 8q24 harboring the C-MYC oncogene, have been noted as one of the most common chromosomal abnormalities in prostate cancer (CaP) progression. However, the frequency of C-MYC alterations in CaP has remained uncertain. A recent study, using a new anti-MYC antibody, described prevalent upregulation of nuclear C-MYC protein expression as an early oncogenic alteration in CaP. Further, we have recently reported regulation of C-MYC expression by ERG and a significant correlation between C-MYC overexpression and TMPRSS2–ERG fusion in early stage CaP. These emerging data suggest that increased C-MYC expression may be a critical and early oncogenic event driving CaP progression. In this study, we assessed whether C-MYC mRNA overexpression in primary prostate tumors was predictive of more aggressive tumor or disease progression. Our approach was to quantitatively determine C-MYC mRNA expression levels in laser capture micro-dissected tumor cells and matched benign epithelial cells in a radical prostatectomy cohort with long follow-up data available. On the basis of our results, we conclude that elevated C-MYC expression in primary prostate tumor is biologically relevant and may be a predictor of future biochemical recurrence.

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References

  1. American Cancer Society: Cancer Facts & Figures 2009. http://www.cancer.org.

  2. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ . Cancer statistics, 2009. Cancer J Clin 2009; 59: 225–249.

    Article  Google Scholar 

  3. Quinn M, Babb P . Patterns and trends in prostate cancer incidence, survival, prevalence and mortality. Part II: individual countries. BJU Int 2002; 90: 174–184.

    Article  CAS  PubMed  Google Scholar 

  4. Bubendorf L, Kononen J, Koivisto P, Schraml P, Moch H, Gasser TC et al. Survey of gene amplifications during prostate cancer progression by high-throughout fluorescence in situ hybridization on tissue microarrays. Cancer Res 1999; 59: 803–806.

    CAS  PubMed  Google Scholar 

  5. De Marzo AM, Platz EA, Sutcliffe S, Xu J, Grönberg H, Drake CG et al. Inflammation in prostate carcinogenesis. Nat Rev Cancer 2007; 7: 256–269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kumar-Sinha C, Tomlins SA, Chinnaiyan AM . Recurrent gene fusions in prostate cancer. Nat Rev Cancer 2008; 8: 491–511.

    Article  Google Scholar 

  7. Gurel B, Iwata T, Koh CM, Yegnasubramanian S, Nelson WG, De Marzo AM . Molecular alterations in prostate cancer as diagnostic, prognostic, and therapeutic agents? Adv Anat Pathol 2008; 15: 319–331.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Quinn DI, Henshall SM, Sutherland RL . Molecular markers of prostate cancer outcome. Eur J Cancer 2005; 41: 858–887.

    Article  CAS  PubMed  Google Scholar 

  9. Williams K, Fernandez S, Stien X, Ishii K, Love HD, Lau YF et al. Unopposed C-MYC expression in benign prostatic epithelium causes a cancer phenotype. Prostate 2005; 63: 369–384.

    Article  CAS  PubMed  Google Scholar 

  10. Vita M, Henriksson M . The Myc oncoprotein as a therapeutic target for human cancer. Semin Cancer Biol 2006; 16: 318–330.

    Article  CAS  PubMed  Google Scholar 

  11. Knoepfler PS . Myc goes global: new tricks for an old oncogene. Cancer Res 2007; 67: 5061–5063.

    Article  CAS  PubMed  Google Scholar 

  12. Gardner LB, Lee LA, Dang CV . C-myc protooncogene. In: Bertino JR (ed). Encyclopedia of Cancer. Elsevier Science: Amsterdam, 2002, pp 555–561.

    Chapter  Google Scholar 

  13. Herold S, Herkert B, Eilers M . Facilitating replication ounder stress: an oncogenic function of MYC? Nat Rev Cancer 2009; 9: 441–444.

    Article  CAS  PubMed  Google Scholar 

  14. Fleming WH, Hamel A, MacDonald R, Ramsey E, Pettigrew NM, Johnston B et al. Expression of the C-MYC protooncogene in human prostatic carcinoma and benign prostatic hyperplasia. Cancer Res 1986; 46: 1535–1538.

    CAS  PubMed  Google Scholar 

  15. Fox SB, Persad RA, Royds J, Kore RN, Silcocks PB, Collins CC . P53 and C-MYC expression in Stage A1 prostatic adenocarcinoma: useful prognostic determinants? J Urol 1993; 150: 490–494.

    Article  CAS  PubMed  Google Scholar 

  16. Jenkins RB, Qian J, Lieber MM, Bostwick DG . Detection of C-MYC oncogene amplification and chromosomal anomalies in metastatic prostatic carcinoma by fluorescence in situ hybridization. Cancer Res 1997; 57: 524–531.

    CAS  PubMed  Google Scholar 

  17. Qian J, Jenkins RB, Bostwick DG . Detection of chromosomal anomalies and C-MYC gene amplification in the cribriform pattern of prostatic intraepithelial neoplasia and carcinoma by fluorescence in situ hybridization. Mod Pathol 1997; 10: 1113–1119.

    CAS  PubMed  Google Scholar 

  18. Sato H, Minei S, Hachiya T, Yoshida T, Takimoto Y . Fluorescence in situ hybridization analysis of C-MYC amplification in Stage T3N0M0 prostate cancer in Japanese patients. Int J Urol 2006; 13: 761–766.

    Article  CAS  PubMed  Google Scholar 

  19. Gurel B, Iwata T, Koh CM, Jenkins RB, Lan F, Van Dang C et al. Nuclear MYC protein overexpression is an early alteration in human prostate carcinogenesis. Mod Pathol 2008; 21: 1156–1167.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Petrovics G, Liu A, Shaheduzzaman S, Furusato B, Sun C, Chen Y et al. Frequent overexpression of ETS-related gene-1 (ERG1) in prostate cancer transcriptome. Oncogene 2005; 24: 3847–3852.

    Article  CAS  PubMed  Google Scholar 

  21. Mwamukonda K, Chen Y, Ravindranath L, Furusato B, Hu Y, Sterbis J et al. Quantitative expression of TMPRSS2 transcript in prostate tumor cells reflects TMPRSS2-ERG fusion status. Prostate Cancer Prostatic Dis 2010; 13: 47–51.

    Article  CAS  PubMed  Google Scholar 

  22. Latil A, Vidaud D, Valéri A, Fournier G, Vidaud M, Lidereau R et al. HTERT expression correlates with MYC over-expression in human prostate cancer. Int J Cancer 2000; 89: 172–176.

    Article  CAS  PubMed  Google Scholar 

  23. Xu LL, Sun C, Petrovics G, Makarem M, Furusato B, Zhang W et al. Quantitative expression profile of PSGR in prostate cancer. Prostate Cancer Prostatic Dis 2006; 9: 56–61.

    Article  CAS  PubMed  Google Scholar 

  24. Sun C, Dobi A, Mohamed A, Li H, Thangapazham RL, Furusato B et al. TMPRSS2-ERG fusion, a common genomic alteration in prostate cancer activates C-MYC and abrogates prostate epithelial differentiation. Oncogene 2008; 27: 5348–5353.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported in part by Grant 5R01 DK065977 for SS and GP from the National Institutes of Health. We thank Dennis Young for her superb assistance with immunohistochemistry experiments.

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The views expressed in this manuscript are those of the authors and do not reflect the official policy of the Department of the Army, Department of Defense or the US Government.

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Correspondence to G Petrovics.

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Supplementary Information accompanies the paper on the Prostate Cancer and Prostatic Diseases website

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Hawksworth, D., Ravindranath, L., Chen, Y. et al. Overexpression of C-MYC oncogene in prostate cancer predicts biochemical recurrence. Prostate Cancer Prostatic Dis 13, 311–315 (2010). https://doi.org/10.1038/pcan.2010.31

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