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New Study Reveals Molecular Underpinnings of Prostate Cancer in Patients of African Descent

A new whole-genome prostate cancer genome resource for sub-Saharan Africa is reported this week in Nature, demonstrating how global inclusion in cancer genomics can unravel unseen heterogeneity in prostate cancer in terms of its genomic and clinical behaviors. Prostate cancer is characterized by considerable geo-ethnic disparity. African ancestry is a significant risk factor for the disease, with 2.7-fold higher mortality rates across sub-Saharan Africa than global averages, yet the genetic and nongenetic factors underlying this is not known. In this week's study, a team led by scientists from the University of Sydney perform whole-genome sequencing of treatment-naïve prostate cancer samples from 183 ancestrally and globally distinct patients to generate a large cancer genomics resource for sub-Saharan Africa that includes around 2 million somatic variants. Findings specific to patients of African ancestry include an elevated tumor mutational burden, increased percentage of genome alteration, a greater number of predicted damaging mutations and a higher total of mutational signatures, and various cancer driver genes. The researchers also describe a molecular taxonomy for prostate cancer differentiated by ancestry and defined as global mutational subtypes, while uncovering different evolutionary trajectories and mutational processes that suggest both common genetic and environmental factors contribute to the disparity between ethnicities. "Our study suggests that larger genomic datasets of geo-ethnically diverse and ancestrally defined populations in a unified analysis will continue to identify rare and geographically restricted subtypes in prostate cancer and potentially other cancers," the study's authors write. "We demonstrate that ancestral and geographical attributes of patients could facilitate … studies on cancer population genomics, an alternative to cancer personalized genomics, for a better scientific understanding of nature versus nurture."

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