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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 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.

SUBMITTER: Zhou W

PROVIDER: S-EPMC10700489 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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

Zhou Weiyin W Fischer Anja A Ogwang Martin D MD Luo Wen W Kerchan Patrick P Reynolds Steven J SJ Tenge Constance N CN Were Pamela A PA Kuremu Robert T RT Wekesa Walter N WN Masalu Nestory N Kawira Esther E Kinyera Tobias T Otim Isaac I Legason Ismail D ID Nabalende Hadijah H Ayers Leona W LW Bhatia Kishor K Goedert James J JJ Gouveia Mateus H MH Cole Nathan N Hicks Belynda B Jones Kristine K Hummel Michael M Schlesner Mathias M Chagaluka George G Mutalima Nora N Borgstein Eric E Liomba George N GN Kamiza Steve S Mkandawire Nyengo N Mitambo Collins C Molyneux Elizabeth M EM Newton Robert R Glaser Selina S Kretzmer Helene H Manning Michelle M Hutchinson Amy A Hsing Ann W AW Tettey Yao Y Adjei Andrew A AA Chanock Stephen J SJ Siebert Reiner R Yeager Meredith M Prokunina-Olsson Ludmila L Machiela Mitchell J MJ Mbulaiteye Sam M SM

Nature communications 20231206 1

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 chromoso ...[more]

PMID: 38057307

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Project description:Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome were significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population. Please note that the data from the comparable cohort of patients in the USUS data was published as supplemental material of PMID: 22760045 but not submitted to GEO The 'patient_info.txt' contains 12 clinical, 7 immunological and 3 microbiological variables for each patient.

Dataset Information

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

Publications

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

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