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Ethnicity and ERG frequency in prostate cancer

Key Points

  • Prevalent ERG oncogene activation (predominantly owing to TMPRSS2–ERG fusion) is one of the most widely studied and validated alterations in a prostate cancer driver gene

  • The majority of studies establishing ERG prevalence in prostate cancer have focused on patients of European ancestry

  • The frequency of ERG-oncoprotein-positive prostate cancers is substantially lower among African American men (20–30%) than among white Americans (50–60%)

  • Frequencies of ERG are lowest (10–20%) in Asian populations, but data are variable across studies and methodologies

  • ERG positive prostate tumour foci are relatively homogenous for immunostaining, but inconsistencies in frequency variations can still result from sampling bias owing to interfocal heterogeneity of ERG in the multifocal context of prostate cancer

  • Detection of TMPRSS2–ERG fusions using fluorescence in situ hybridization, or of ERG oncoprotein using immunohistochemistry, are highly concordant, but immunohistochemistry demonstrates less variability and might be more applicable for clinical use

Abstract

Emerging observations emphasize a distinct biology of prostate cancer among men of different ethnicities and races, as demonstrated by remarkable differences in the frequency of ERG oncogenic activation, one of the most common and widely studied prostate cancer driver genes. Worldwide assessment of ERG alterations frequencies show consistent trends, with men of European ancestry having the highest rates of alteration and men of African or Asian ancestries having considerably lower alteration rates. However, data must be interpreted cautiously, owing to variations in assay platforms and specimen types, as well as ethnic and geographical classifications. Many opportunities and challenges remain in assessing cancer-associated molecular alterations at a global level, and these need to be addressed in order to realize the true potential of precision medicine for all cancer patients.

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Figure 1: TMPRSS2 is actively transcribed under the control of the androgen receptor (AR) on chromosome 21q22.3 (depicted on the negative DNA strand in telomeric position relative to ERG).
Figure 2: Developing direct and indirect approaches to target ERG-positive prostate tumours.
Figure 3: Reported ERG frequencies worldwide.

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Acknowledgements

Authors express sincere thanks to Mr. Stephen Doyle for the art work. The opinions or assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of Defense, the Uniformed Services University of the Health Sciences or any other agency of the U.S. Government.

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All authors researched data for article; A. D., J. S. and S. S. made substantial contributions to discussion of content; A. D., J. S., M. D. and S.S. wrote the manuscript, and A. D. and S. S. reviewed and edited the manuscript before submission.

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Correspondence to Shiv Srivastava or Albert Dobi.

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Competing interests

S. S. and A. D. are inventors of the ERG monoclonal antibody (9FY) that is licensed to Biocare Medical by The Henry M. Jackson Foundation for the Advancement of Military Medicine. The other authors declare no competing interests.

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Sedarsky, J., Degon, M., Srivastava, S. et al. Ethnicity and ERG frequency in prostate cancer. Nat Rev Urol 15, 125–131 (2018). https://doi.org/10.1038/nrurol.2017.140

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