An Elevated Rate of Whole-Genome Duplication in Cancers from Black Patients

In the United States, Black individuals have higher rates of cancer mortality than any other racial or ethnic group. The sources of these significant racial disparities are not fully understood, and may include social, environmental, and genetic factors that influence cancer onset, diagnosis, and treatment. Here, we examined genomic data from several large-scale cancer patient cohorts to search for racial associations in chromosome copy number alterations. We found that tumors from Black patients were significantly more likely to exhibit whole-genome duplications (WGDs), a genomic event that enhances metastasis and aggressive disease, compared to tumors from white patients. Among patients with WGD-positive cancers, there was no significant difference in survival between Black and white patients, suggesting that the increased incidence of WGD events could contribute to the disparities in patient outcome. Genomic analysis identified several somatic alterations associated with WGD events that were consistent between Black and white populations, indicating that the increase in WGD events may be driven by environmental or epigenetic factors in Black patients. In total, these findings identify a class of genomic alterations that may influence racial disparities in cancer patient outcome. As cancers that have undergone WGD events exhibit unique genetic vulnerabilities, therapies that selectively target WGD-positive cancers may be particularly effective at treating aggressive malignancies in Black patients. ### Competing Interest Statement J.M.S. has received consulting fees from Merck, Pfizer, Ono Pharmaceuticals, and Highside Capital Management, is a member of the advisory boards of Tyra Biosciences, BioIO, and the Chemical Probes Portal, and is a co-founder of Meliora Therapeutics. ### Funding Statement Research in the Sheltzer Lab is supported by NIH grants R01CA237652 and R01CA276666, Department of Defense grant W81XWH-20-1-068, an American Cancer Society Research Scholar Grant, a Breast Cancer Alliance Young Investigator Award, a sponsored research agreement from Ono Pharmaceuticals, and a sponsored research agreement from Meliora Therapeutics. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study used only data available from TCGA, MSK-MET, and PCAWG. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data referenced in the manuscript are publicly available.