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TMPRSS2‐ERG fusions linked to prostate cancer racial health disparities: A focus on Africa

BACKGROUND: The androgen‐regulated gene TMPRSS2 to the ETS transcription factor gene ERG fusion is the most common genomic alteration acquired during prostate tumorigenesis and biased toward men of European ancestry. In contrast, African American men present with more advanced disease, yet their tum...

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Autores principales: Blackburn, James, Vecchiarelli, Stefano, Heyer, Erin E., Patrick, Sean M., Lyons, Ruth J., Jaratlerdsiri, Weerachai, van Zyl, Smit, Bornman, M. S. Riana, Mercer, Tim R., Hayes, Vanessa M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617820/
https://www.ncbi.nlm.nih.gov/pubmed/31090091
http://dx.doi.org/10.1002/pros.23823
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author Blackburn, James
Vecchiarelli, Stefano
Heyer, Erin E.
Patrick, Sean M.
Lyons, Ruth J.
Jaratlerdsiri, Weerachai
van Zyl, Smit
Bornman, M. S. Riana
Mercer, Tim R.
Hayes, Vanessa M.
author_facet Blackburn, James
Vecchiarelli, Stefano
Heyer, Erin E.
Patrick, Sean M.
Lyons, Ruth J.
Jaratlerdsiri, Weerachai
van Zyl, Smit
Bornman, M. S. Riana
Mercer, Tim R.
Hayes, Vanessa M.
author_sort Blackburn, James
collection PubMed
description BACKGROUND: The androgen‐regulated gene TMPRSS2 to the ETS transcription factor gene ERG fusion is the most common genomic alteration acquired during prostate tumorigenesis and biased toward men of European ancestry. In contrast, African American men present with more advanced disease, yet their tumors are less likely to acquire TMPRSS2‐ERG. Data for Africa is scarce. METHODS: RNA was made available for genomic analyses from 181 prostate tissue biopsy cores from Black South African men, 94 with and 87 without pathological evidence for prostate cancer. Reverse transcription polymerase chain reaction was used to screen for the TMPRSS2‐ERG fusion, while transcript junction coordinates and isoform frequencies, including novel gene fusions, were determined using targeted RNA sequencing. RESULTS: Here we report a frequency of 13% for TMPRSS2‐ERG in tumors from Black South Africans. Present in 12/94 positive versus 1/87 cancer negative prostate tissue cores, this suggests a 92.62% predictivity for a positive cancer diagnosis (P = 0.0031). At a frequency of almost half that reported for African Americans and roughly a quarter of that reported for men of European ancestry, acquisition of TMPRSS2‐ERG appears to be inversely associated with aggressive prostate cancer. Further support was provided by linking the presence of TMPRSS2‐ERG to low‐grade disease in younger patients (P = 0.0466), with higher expressing distal ERG fusion junction coordinates. CONCLUSIONS: Only the second study of its kind for the African continent, we support a link between TMPRSS2‐ERG status and prostate cancer racial health disparity beyond the borders of the United States. We call for urgent evaluation of androgen deprivation therapy within Africa.
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spelling pubmed-66178202019-07-22 TMPRSS2‐ERG fusions linked to prostate cancer racial health disparities: A focus on Africa Blackburn, James Vecchiarelli, Stefano Heyer, Erin E. Patrick, Sean M. Lyons, Ruth J. Jaratlerdsiri, Weerachai van Zyl, Smit Bornman, M. S. Riana Mercer, Tim R. Hayes, Vanessa M. Prostate Rapid Communication BACKGROUND: The androgen‐regulated gene TMPRSS2 to the ETS transcription factor gene ERG fusion is the most common genomic alteration acquired during prostate tumorigenesis and biased toward men of European ancestry. In contrast, African American men present with more advanced disease, yet their tumors are less likely to acquire TMPRSS2‐ERG. Data for Africa is scarce. METHODS: RNA was made available for genomic analyses from 181 prostate tissue biopsy cores from Black South African men, 94 with and 87 without pathological evidence for prostate cancer. Reverse transcription polymerase chain reaction was used to screen for the TMPRSS2‐ERG fusion, while transcript junction coordinates and isoform frequencies, including novel gene fusions, were determined using targeted RNA sequencing. RESULTS: Here we report a frequency of 13% for TMPRSS2‐ERG in tumors from Black South Africans. Present in 12/94 positive versus 1/87 cancer negative prostate tissue cores, this suggests a 92.62% predictivity for a positive cancer diagnosis (P = 0.0031). At a frequency of almost half that reported for African Americans and roughly a quarter of that reported for men of European ancestry, acquisition of TMPRSS2‐ERG appears to be inversely associated with aggressive prostate cancer. Further support was provided by linking the presence of TMPRSS2‐ERG to low‐grade disease in younger patients (P = 0.0466), with higher expressing distal ERG fusion junction coordinates. CONCLUSIONS: Only the second study of its kind for the African continent, we support a link between TMPRSS2‐ERG status and prostate cancer racial health disparity beyond the borders of the United States. We call for urgent evaluation of androgen deprivation therapy within Africa. John Wiley and Sons Inc. 2019-05-15 2019-07-01 /pmc/articles/PMC6617820/ /pubmed/31090091 http://dx.doi.org/10.1002/pros.23823 Text en © 2019 The Authors. The Prostate Published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Rapid Communication
Blackburn, James
Vecchiarelli, Stefano
Heyer, Erin E.
Patrick, Sean M.
Lyons, Ruth J.
Jaratlerdsiri, Weerachai
van Zyl, Smit
Bornman, M. S. Riana
Mercer, Tim R.
Hayes, Vanessa M.
TMPRSS2‐ERG fusions linked to prostate cancer racial health disparities: A focus on Africa
title TMPRSS2‐ERG fusions linked to prostate cancer racial health disparities: A focus on Africa
title_full TMPRSS2‐ERG fusions linked to prostate cancer racial health disparities: A focus on Africa
title_fullStr TMPRSS2‐ERG fusions linked to prostate cancer racial health disparities: A focus on Africa
title_full_unstemmed TMPRSS2‐ERG fusions linked to prostate cancer racial health disparities: A focus on Africa
title_short TMPRSS2‐ERG fusions linked to prostate cancer racial health disparities: A focus on Africa
title_sort tmprss2‐erg fusions linked to prostate cancer racial health disparities: a focus on africa
topic Rapid Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617820/
https://www.ncbi.nlm.nih.gov/pubmed/31090091
http://dx.doi.org/10.1002/pros.23823
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