Abstract:
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.
