An elevated rate of whole-genome duplications in cancers from Black patients

Leanne M. Brown, Ryan A. Hagenson, Tilen Koklič, Iztok Urbančič, Lu Qiao, Janez Strancar and Jason M. Sheltzer ()
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Leanne M. Brown: Yale University, School of Medicine
Ryan A. Hagenson: Yale University, School of Medicine
Tilen Koklič: Jožef Stefan Institute
Iztok Urbančič: Jožef Stefan Institute
Lu Qiao: Yale University, School of Medicine
Janez Strancar: Jožef Stefan Institute
Jason M. Sheltzer: Yale University, School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract In the United States, Black individuals have higher rates of cancer mortality than any other racial group. Here, we examine chromosome copy number changes in cancers from more than 1800 self-reported Black patients. We find that tumors from self-reported Black patients are significantly more likely to exhibit whole-genome duplications (WGDs), a genomic event that enhances metastasis and aggressive disease, compared to tumors from self-reported white patients. This increase in WGD frequency is observed across multiple cancer types, including breast, endometrial, and lung cancer, and is associated with shorter patient survival. We further demonstrate that combustion byproducts are capable of inducing WGDs in cell culture, and cancers from self-reported Black patients exhibit mutational signatures consistent with exposure to these carcinogens. In total, these findings identify a type of genomic alteration that is associated with environmental exposures and that may influence racial disparities in cancer outcomes.

Date: 2024
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DOI: 10.1038/s41467-024-52554-5

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