Kataegis, the focal hypermutation of single base substitutions (SBS) in tumour genomes, has received little attention with respect to prostate cancer (PCa) associated molecular and clinical features. Most notably, data is lacking with regards to this tumour evolutionary phenomenon and PCa racial disparities, with African men disproportionately impacted. Here through comparison between African (n = 109) and non-African (n = 79) whole genome sequenced treatment naïve primary tumours, using a single analytical workflow we assessed for shared and unique features of kataegis. Linking kataegis to aggressive presentation, structural variant burden and copy number loss, we attributed APOBEC3 activity through higher rates of SBS2 to high-risk African tumours. While kataegis positive African patients presented with elevated prostate specific antigen levels, their tumours showed evolutionary unique trajectories marked by increased subclonal and structural variant-independent kataegis. The potential to exacerbate tumour heterogeneity emphases the significance of continued exploration of biological behaviours and environmental exposures for African patients.
Research square. 2024 Jun 28*** epublish ***
Vanessa Hayes, Jue Jiang, Avraam Tapinos, Ruotian Huang, Riana Bornman, Phillip Stricker, Shingai Mutambirwa, David Wedge, Weerachai Jaratlerdsiri
University of Sydney., Garvan Institute of Medical Research., University of Manchester., University of Pretoria., St. Vincent's Hospital., Sefako Makgatho Health Science University.