Mosaic chromosomal alterations in peripheral blood leukocytes of children in sub-Saharan Africa

Weiyin Zhou, Anja Fischer, Martin D. Ogwang, Wen Luo, Patrick Kerchan, Steven J. Reynolds, Constance N. Tenge, Pamela A. Were, Robert T. Kuremu, Walter N. Wekesa, Nestory Masalu, Esther Kawira, Tobias Kinyera, Isaac Otim, Ismail D. Legason, Hadijah Nabalende, Leona W. Ayers, Kishor Bhatia, James J. Goedert, Mateus H. Gouveia, Nathan Cole, Belynda Hicks, Kristine Jones, Michael Hummel, Mathias Schlesner, George Chagaluka, Nora Mutalima, Eric Borgstein, George N. Liomba, Steve Kamiza, Nyengo Mkandawire, Collins Mitambo, Elizabeth M. Molyneux, Robert Newton, Selina Glaser, Helene Kretzmer, Michelle Manning, Amy Hutchinson, Ann W. Hsing, Yao Tettey, Andrew A. Adjei, Stephen J. Chanock, Reiner Siebert, Meredith Yeager, Ludmila Prokunina-Olsson, Mitchell J. Machiela and Sam M. Mbulaiteye ()
Additional contact information
Weiyin Zhou: Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services
Anja Fischer: Ulm University and Ulm University Medical Center
Martin D. Ogwang: EMBLEM Study, St. Mary’s Hospital, Lacor
Wen Luo: Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services
Patrick Kerchan: EMBLEM Study, Kuluva Hospital
Steven J. Reynolds: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Constance N. Tenge: Moi University College of Health Sciences
Pamela A. Were: EMBLEM Study, Academic Model Providing Access To Healthcare (AMPATH)
Robert T. Kuremu: Moi University College of Health Sciences
Walter N. Wekesa: Moi University College of Health Sciences
Nestory Masalu: EMBLEM Study, Bugando Medical Center
Esther Kawira: EMBLEM Study, Shirati Health, Education, and Development Foundation
Tobias Kinyera: EMBLEM Study, St. Mary’s Hospital, Lacor
Isaac Otim: EMBLEM Study, St. Mary’s Hospital, Lacor
Ismail D. Legason: EMBLEM Study, Kuluva Hospital
Hadijah Nabalende: EMBLEM Study, St. Mary’s Hospital, Lacor
Leona W. Ayers: The Ohio State University
Kishor Bhatia: Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services
James J. Goedert: Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services
Mateus H. Gouveia: Center for Research on Genomics & Global Health, NHGRI, National Institutes of Health
Nathan Cole: Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services
Belynda Hicks: Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services
Kristine Jones: Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services
Michael Hummel: Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin
Mathias Schlesner: University of Augsburg
George Chagaluka: University of Malawi
Nora Mutalima: University of York
Eric Borgstein: University of Malawi
George N. Liomba: University of Malawi
Steve Kamiza: University of Malawi
Nyengo Mkandawire: University of Malawi
Collins Mitambo: Research Department, Ministry of Health
Elizabeth M. Molyneux: University of Malawi
Robert Newton: University of York
Selina Glaser: Ulm University and Ulm University Medical Center
Helene Kretzmer: Max Planck Institute for Molecular Genetics
Michelle Manning: Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services
Amy Hutchinson: Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services
Ann W. Hsing: Stanford University
Yao Tettey: Department of Pathology, University of Ghana Medical School, College of Health Sciences
Andrew A. Adjei: Department of Pathology, University of Ghana Medical School, College of Health Sciences
Stephen J. Chanock: Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services
Reiner Siebert: Ulm University and Ulm University Medical Center
Meredith Yeager: Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services
Ludmila Prokunina-Olsson: Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services
Mitchell J. Machiela: Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services
Sam M. Mbulaiteye: Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract In high-income countries, mosaic chromosomal alterations in peripheral blood leukocytes are associated with an elevated risk of adverse health outcomes, including hematologic malignancies. We investigate mosaic chromosomal alterations in sub-Saharan Africa among 931 children with Burkitt lymphoma, an aggressive lymphoma commonly characterized by immunoglobulin-MYC chromosomal rearrangements, 3822 Burkitt lymphoma-free children, and 674 cancer-free men from Ghana. We find autosomal and X chromosome mosaic chromosomal alterations in 3.4% and 1.7% of Burkitt lymphoma-free children, and 8.4% and 3.7% of children with Burkitt lymphoma (P-values = 5.7×10−11 and 3.74×10−2, respectively). Autosomal mosaic chromosomal alterations are detected in 14.0% of Ghanaian men and increase with age. Mosaic chromosomal alterations in Burkitt lymphoma cases include gains on chromosomes 1q and 8, the latter spanning MYC, while mosaic chromosomal alterations in Burkitt lymphoma-free children include copy-neutral loss of heterozygosity on chromosomes 10, 14, and 16. Our results highlight mosaic chromosomal alterations in sub-Saharan African populations as a promising area of research.

Date: 2023
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DOI: 10.1038/s41467-023-43881-0

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