Mosaic chromosomal alterations in peripheral blood leukocytes of children in sub-Saharan Africa
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 ly...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-12-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-43881-0 |
| _version_ | 1797397908974206976 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Weiyin Zhou |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T01:17:01Z |
| format | Article |
| id | doaj.art-d757f218f82541a7abe121d8c91e7678 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-09T01:17:01Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-d757f218f82541a7abe121d8c91e76782023-12-10T12:25:06ZengNature PortfolioNature Communications2041-17232023-12-0114111310.1038/s41467-023-43881-0Mosaic chromosomal alterations in peripheral blood leukocytes of children in sub-Saharan AfricaWeiyin Zhou0Anja Fischer1Martin D. Ogwang2Wen Luo3Patrick Kerchan4Steven J. Reynolds5Constance N. Tenge6Pamela A. Were7Robert T. Kuremu8Walter N. Wekesa9Nestory Masalu10Esther Kawira11Tobias Kinyera12Isaac Otim13Ismail D. Legason14Hadijah Nabalende15Leona W. Ayers16Kishor Bhatia17James J. Goedert18Mateus H. Gouveia19Nathan Cole20Belynda Hicks21Kristine Jones22Michael Hummel23Mathias Schlesner24George Chagaluka25Nora Mutalima26Eric Borgstein27George N. Liomba28Steve Kamiza29Nyengo Mkandawire30Collins Mitambo31Elizabeth M. Molyneux32Robert Newton33Selina Glaser34Helene Kretzmer35Michelle Manning36Amy Hutchinson37Ann W. Hsing38Yao Tettey39Andrew A. Adjei40Stephen J. Chanock41Reiner Siebert42Meredith Yeager43Ludmila Prokunina-Olsson44Mitchell J. Machiela45Sam M. Mbulaiteye46Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human ServicesInstitute of Human Genetics, Ulm University and Ulm University Medical CenterEMBLEM Study, St. Mary’s Hospital, LacorDivision of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human ServicesEMBLEM Study, Kuluva HospitalDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthEMBLEM Study, Moi University College of Health SciencesEMBLEM Study, Academic Model Providing Access To Healthcare (AMPATH)EMBLEM Study, Moi University College of Health SciencesEMBLEM Study, Moi University College of Health SciencesEMBLEM Study, Bugando Medical CenterEMBLEM Study, Shirati Health, Education, and Development FoundationEMBLEM Study, St. Mary’s Hospital, LacorEMBLEM Study, St. Mary’s Hospital, LacorEMBLEM Study, Kuluva HospitalEMBLEM Study, St. Mary’s Hospital, LacorDepartment of Pathology, The Ohio State UniversityDivision of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human ServicesDivision of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human ServicesCenter for Research on Genomics & Global Health, NHGRI, National Institutes of HealthDivision of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human ServicesDivision of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human ServicesDivision of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human ServicesCharité - Universitätsmedizin Berlin, corporate member of Freie Universität BerlinBiomedical Informatics, Data Mining and Data Analytics, University of AugsburgDepartments of Pediatrics and Surgery, College of Medicine, University of MalawiEpidemiology and Cancer Statistics Group, Department of Health Sciences, University of YorkDepartments of Pediatrics and Surgery, College of Medicine, University of MalawiDepartments of Pediatrics and Surgery, College of Medicine, University of MalawiDepartments of Pediatrics and Surgery, College of Medicine, University of MalawiDepartments of Pediatrics and Surgery, College of Medicine, University of MalawiResearch Department, Ministry of HealthDepartments of Pediatrics and Surgery, College of Medicine, University of MalawiEpidemiology and Cancer Statistics Group, Department of Health Sciences, University of YorkInstitute of Human Genetics, Ulm University and Ulm University Medical CenterDepartment of Genome Regulation, Max Planck Institute for Molecular GeneticsDivision of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human ServicesDivision of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human ServicesStanford Cancer Institute, Stanford UniversityDepartment of Pathology, University of Ghana Medical School, College of Health SciencesDepartment of Pathology, University of Ghana Medical School, College of Health SciencesDivision of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human ServicesInstitute of Human Genetics, Ulm University and Ulm University Medical CenterDivision of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human ServicesDivision of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human ServicesDivision of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human ServicesDivision of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, US Department of Health and Human ServicesAbstract 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.https://doi.org/10.1038/s41467-023-43881-0 |
| spellingShingle | 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 Mosaic chromosomal alterations in peripheral blood leukocytes of children in sub-Saharan Africa Nature Communications |
| title | Mosaic chromosomal alterations in peripheral blood leukocytes of children in sub-Saharan Africa |
| title_full | Mosaic chromosomal alterations in peripheral blood leukocytes of children in sub-Saharan Africa |
| title_fullStr | Mosaic chromosomal alterations in peripheral blood leukocytes of children in sub-Saharan Africa |
| title_full_unstemmed | Mosaic chromosomal alterations in peripheral blood leukocytes of children in sub-Saharan Africa |
| title_short | Mosaic chromosomal alterations in peripheral blood leukocytes of children in sub-Saharan Africa |
| title_sort | mosaic chromosomal alterations in peripheral blood leukocytes of children in sub saharan africa |
| url | https://doi.org/10.1038/s41467-023-43881-0 |
| work_keys_str_mv | AT weiyinzhou mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT anjafischer mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT martindogwang mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT wenluo mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT patrickkerchan mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT stevenjreynolds mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT constancentenge mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT pamelaawere mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT roberttkuremu mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT walternwekesa mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT nestorymasalu mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT estherkawira mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT tobiaskinyera mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT isaacotim mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT ismaildlegason mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT hadijahnabalende mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT leonawayers mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT kishorbhatia mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT jamesjgoedert mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT mateushgouveia mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT nathancole mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT belyndahicks mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT kristinejones mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT michaelhummel mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT mathiasschlesner mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT georgechagaluka mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT noramutalima mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT ericborgstein mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT georgenliomba mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT stevekamiza mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT nyengomkandawire mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT collinsmitambo mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT elizabethmmolyneux mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT robertnewton mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT selinaglaser mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT helenekretzmer mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT michellemanning mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT amyhutchinson mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT annwhsing mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT yaotettey mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT andrewaadjei mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT stephenjchanock mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT reinersiebert mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT meredithyeager mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT ludmilaprokuninaolsson mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT mitchelljmachiela mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica AT sammmbulaiteye mosaicchromosomalalterationsinperipheralbloodleukocytesofchildreninsubsaharanafrica |