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; Sam M Mbulaiteye

doi:10.1038/s41467-023-43881-0

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

Nat Commun. 2023 Dec 6;14(1):8081. doi: 10.1038/s41467-023-43881-0.

Authors

Weiyin Zhou^{1

2}, Anja Fischer³, Martin D Ogwang⁴, Wen Luo^{1

2}, Patrick Kerchan⁵, Steven J Reynolds⁶, Constance N Tenge⁷, Pamela A Were⁸, Robert T Kuremu⁷, Walter N Wekesa⁷, Nestory Masalu⁹, Esther Kawira¹⁰, Tobias Kinyera^{4

11}, Isaac Otim^{4

11}, Ismail D Legason^{5

11}, Hadijah Nabalende^{4

11}, Leona W Ayers¹², Kishor Bhatia¹, James J Goedert¹, Mateus H Gouveia¹³, Nathan Cole^{1

2}, Belynda Hicks^{1

2}, Kristine Jones^{1

2}, Michael Hummel^{14

15}, Mathias Schlesner¹⁶, George Chagaluka¹⁷, Nora Mutalima^{18

19}, Eric Borgstein¹⁷, George N Liomba¹⁷, Steve Kamiza¹⁷, Nyengo Mkandawire¹⁷, Collins Mitambo²⁰, Elizabeth M Molyneux¹⁷, Robert Newton¹⁸, Selina Glaser³, Helene Kretzmer²¹, Michelle Manning^{1

2}, Amy Hutchinson^{1

2}, Ann W Hsing²², Yao Tettey²³, Andrew A Adjei²³, Stephen J Chanock^{1

2}, Reiner Siebert³, Meredith Yeager^{1

2}, Ludmila Prokunina-Olsson¹, Mitchell J Machiela¹, Sam M Mbulaiteye²⁴

Affiliations

¹ Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD, USA.
² Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
³ Institute of Human Genetics, Ulm University and Ulm University Medical Center, Ulm, Germany.
⁴ EMBLEM Study, St. Mary's Hospital, Lacor, Gulu, Uganda.
⁵ EMBLEM Study, Kuluva Hospital, Arua, Uganda.
⁶ Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
⁷ EMBLEM Study, Moi University College of Health Sciences, Eldoret, Kenya.
⁸ EMBLEM Study, Academic Model Providing Access To Healthcare (AMPATH), Eldoret, Kenya.
⁹ EMBLEM Study, Bugando Medical Center, Mwanza, Tanzania.
¹⁰ EMBLEM Study, Shirati Health, Education, and Development Foundation, Shirati, Tanzania.
¹¹ EMBLEM Study, African Field Epidemiology Network, Kampala, Uganda.
¹² Department of Pathology, The Ohio State University, Columbus, OH, USA.
¹³ Center for Research on Genomics & Global Health, NHGRI, National Institutes of Health, Bethesda, MD, USA.
¹⁴ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Berlin, Germany.
¹⁵ Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Pathology, D-10117, Berlin, Germany.
¹⁶ Biomedical Informatics, Data Mining and Data Analytics, University of Augsburg, Augsburg, Germany.
¹⁷ Departments of Pediatrics and Surgery, College of Medicine, University of Malawi, Blantyre, Malawi.
¹⁸ Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, York, UK.
¹⁹ Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
²⁰ Research Department, Ministry of Health, P.O. Box 30377, Lilongwe 3, Malawi.
²¹ Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
²² Stanford Cancer Institute, Stanford University, Stanford, Palo Alto, CA, USA.
²³ Department of Pathology, University of Ghana Medical School, College of Health Sciences, P.O. Box KB 52, Korle-Bu, Accra, Ghana.
²⁴ Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD, USA. mbulaits@mail.nih.gov.

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.

MeSH terms

Burkitt Lymphoma* / genetics
Burkitt Lymphoma* / pathology
Child
Chromosome Aberrations
Ghana
Humans
Immunoglobulins / genetics
Leukocytes / pathology
Male
Translocation, Genetic

Substances

Immunoglobulins

Abstract

MeSH terms

Substances

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