African-specific molecular taxonomy of prostate cancer

Weerachai Jaratlerdsiri, Jue Jiang, Tingting Gong, Sean M. Patrick, Cali Willet, Tracy Chew, Ruth J. Lyons, Anne-Maree Haynes, Gabriela Pasqualim, Melanie Louw, James G. Kench, Raymond Campbell, Lisa G. Horvath, Eva K. F. Chan, David C. Wedge, Rosemarie Sadsad, Ilma Simoni Brum, Shingai B. A. Mutambirwa, Phillip D. Stricker, M. S. Riana Bornman and Vanessa M. Hayes ()
Additional contact information
Weerachai Jaratlerdsiri: University of Sydney
Jue Jiang: University of Sydney
Tingting Gong: University of Sydney
Sean M. Patrick: University of Pretoria
Cali Willet: University of Sydney
Tracy Chew: University of Sydney
Ruth J. Lyons: Garvan Institute of Medical Research
Anne-Maree Haynes: Garvan Institute of Medical Research
Gabriela Pasqualim: Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul
Melanie Louw: National Health Laboratory Services
James G. Kench: Royal Prince Alfred Hospital and Central Clinical School, University of Sydney
Raymond Campbell: Kalafong Academic Hospital
Lisa G. Horvath: Garvan Institute of Medical Research
Eva K. F. Chan: Garvan Institute of Medical Research
David C. Wedge: University of Manchester
Rosemarie Sadsad: University of Sydney
Ilma Simoni Brum: Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul
Shingai B. A. Mutambirwa: Sefako Makgatho Health Science University, Dr George Mukhari Academic Hospital
Phillip D. Stricker: Garvan Institute of Medical Research
M. S. Riana Bornman: University of Pretoria
Vanessa M. Hayes: University of Sydney

Nature, 2022, vol. 609, issue 7927, 552-559

Abstract: Abstract Prostate cancer is characterized by considerable geo-ethnic disparity. African ancestry is a significant risk factor, with mortality rates across sub-Saharan Africa of 2.7-fold higher than global averages1. The contributing genetic and non-genetic factors, and associated mutational processes, are unknown2,3. Here, through whole-genome sequencing of treatment-naive prostate cancer samples from 183 ancestrally (African versus European) and globally distinct patients, we generate a large cancer genomics resource for sub-Saharan Africa, identifying around 2 million somatic variants. Significant African-ancestry-specific findings include an elevated tumour mutational burden, increased percentage of genome alteration, a greater number of predicted damaging mutations and a higher total of mutational signatures, and the driver genes NCOA2, STK19, DDX11L1, PCAT1 and SETBP1. Examining all somatic mutational types, we describe a molecular taxonomy for prostate cancer differentiated by ancestry and defined as global mutational subtypes (GMS). By further including Chinese Asian data, we confirm that GMS-B (copy-number gain) and GMS-D (mutationally noisy) are specific to African populations, GMS-A (mutationally quiet) is universal (all ethnicities) and the African–European-restricted subtype GMS-C (copy-number losses) predicts poor clinical outcomes. In addition to the clinical benefit of including individuals of African ancestry, our GMS subtypes reveal different evolutionary trajectories and mutational processes suggesting that both common genetic and environmental factors contribute to the disparity between ethnicities. Analogous to gene–environment interaction—defined here as a different effect of an environmental surrounding in people with different ancestries or vice versa—we anticipate that GMS subtypes act as a proxy for intrinsic and extrinsic mutational processes in cancers, promoting global inclusion in landmark studies.

Date: 2022
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41586-022-05154-6 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:609:y:2022:i:7927:d:10.1038_s41586-022-05154-6

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-022-05154-6

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().