African inclusion in prostate cancer genomic studies provides the first glimpses into addressing health disparities through tailored clinical care

Abstract

became the first African to contribute his complete genome to science. 1 His vision, African inclusion in the benefits of genomic medicine. Spending a lifetime fighting for equality, this was another battle where Africa and its peoples remain disproportionately excluded. But there was more to Tutu's vision. Over a decade earlier, at age 66 years, he had been diagnosed with advanced prostate cancer (PCa). Aware that his southern African ethnicity and genetic ancestral heritage placed him at a significant almost 3-fold increased global risk for associated mortality, 2 he was grateful to the team of doctors around the world who fought his battle alongside him, which he sadly lost on 26 December 2021.While the average man from Sub-Saharan Africa has limited to no access to current advances in PCa care, conversely, this care has almost exclusively been based on research derived from men of European ancestry. Till now, we have had no understanding of the knowledge gainedThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

The impact of telomere length on prostate cancer aggressiveness, genomic instability and health disparities

“…Shared between the ancestries, we found shortened TTL to be associated with acquired variation within the DNA replication tumour-associated gene SETBP1 . Having previously reported SETBP1 to be significantly mutated in African-derived tumours 9 , this new PCa driver 36 showing favourable outcomes in response to immune checkpoint inhibitor treatment in melanoma patients 37 , warrants further investigation on the clinical impact for patients presenting with shortened TTL and SETBP1 mutant prostate tumours. European specific correlations with shortened TTL most notably included: the DNA mismatch repair gene MSH2 , known to be associated with telomere shortening 38 ; PTEN and TP53 tumour suppressor gene deficiencies, consistent with 2012 findings showing their critical roles in telomere dysfunction which aggravates aggressive PCa progression 39 ; while the association with the newly described African-predominant PCa driver DDX11L1 9 remains unexplained.…”

Optical genome mapping reveals balanced and unbalanced genetic changes associated with tumor‐forming potential in an early‐stage prostate cancer epithelial subline (M2205)

“…A comparison of the OGM data to the NGS data showed agreement between the assays, with both methods showing no evidence for an ERG fusion (TMPRSS2::ERG) or mutations of the PICK3A gene, which are findings that are associated with prostate cancer in tumors from White males, but are less frequent/ lacking in tumors from Black patients (Hayes et al, 2023;Jaratlerdsiri et al, 2018;Shim et al, 2022). Of note, the fusion detected by OGM (DEPTOR::TRAPPC9) was not covered on the NGS panel and, therefore, was not validated by an orthogonal method.…”

The impact of telomere length on prostate cancer aggressiveness, genomic instability and health disparities

“…Shared between the ancestries, we found shortened TTL to be associated with acquired variation within the DNA replication tumour-associated gene SETBP1. Having previously reported SETBP1 to be signi cantly mutated in African-derived tumours [9], this new PCa driver [32] showing favourable outcomes in response to immune checkpoint inhibitor treatment in melanoma patients [33], warrants further investigation on the clinical impact for patients presenting with shortened TTL and SETBP1 mutant prostate tumours. European speci c correlations with shortened TTL most notably included: the DNA mismatch repair gene MSH2, known to be associated with telomere shortening [34]; PTEN and TP53 tumour suppressor gene de ciencies, consistent with 2012 ndings showing their critical roles in telomere dysfunction which aggravates aggressive PCa progression [35]; while the association with the newly described African-predominant PCa driver DDX11L1 [9] remains unexplained.…”