Shared genomic features of HIV+ diffuse large B-cell lymphoma in two African cohorts

Abstract The number of people with HIV (PWH) in Africa is rising due to population growth and antiretroviral therapy (ART) availability, with diffuse large B-cell lymphoma (DLBCL) a major cause of mortality. HIV and ART alter DLBCL tumor biology, but few studies of DLBCL include PWH or African patie...

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Main Authors: Sophia M. Roush, Mishalan Moodley, Jenny Coelho, Samantha Beck, Amon Chirwa, Edwards Kasonkanji, Marriam Mponda, Maurice Mulenga, Tamiwe Tomoka, Hanri van Zijl, Katherine Hodkinson, Arshad Ismail, Senzo Mtshali, Jonathan Featherston, Satish Gopal, Matthew S. Painschab, Jenifer Vaughan, Yuri Fedoriw
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-10529-6
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author Sophia M. Roush
Mishalan Moodley
Jenny Coelho
Samantha Beck
Amon Chirwa
Edwards Kasonkanji
Marriam Mponda
Maurice Mulenga
Tamiwe Tomoka
Hanri van Zijl
Katherine Hodkinson
Arshad Ismail
Senzo Mtshali
Jonathan Featherston
Satish Gopal
Matthew S. Painschab
Jenifer Vaughan
Yuri Fedoriw
author_facet Sophia M. Roush
Mishalan Moodley
Jenny Coelho
Samantha Beck
Amon Chirwa
Edwards Kasonkanji
Marriam Mponda
Maurice Mulenga
Tamiwe Tomoka
Hanri van Zijl
Katherine Hodkinson
Arshad Ismail
Senzo Mtshali
Jonathan Featherston
Satish Gopal
Matthew S. Painschab
Jenifer Vaughan
Yuri Fedoriw
author_sort Sophia M. Roush
collection DOAJ
description Abstract The number of people with HIV (PWH) in Africa is rising due to population growth and antiretroviral therapy (ART) availability, with diffuse large B-cell lymphoma (DLBCL) a major cause of mortality. HIV and ART alter DLBCL tumor biology, but few studies of DLBCL include PWH or African patients, limiting translation of emerging treatment strategies. Here, we performed whole exome sequencing of 48 tumors (40 HIV-positive [HIV+]) with paired germline of DLBCL patients from Malawi and South Africa. HIV + DLBCL tumors had distinct mutations depending on ART exposure, and there were several recurrent deleterious variants, with ANKRD11 mutations being prognostic. One tumor from each cohort had high tumor mutational burden and microsatellite-instability with PMS2 and ARID1A mutation. These findings suggest shared genomic characteristics among HIV + DLBCL in Africa, offering opportunities for tailored biomarkers and therapeutic targets for this underserved population.
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spelling doaj-art-cbb942e6acba416cbffb10591b3710d22025-08-20T03:05:18ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-10529-6Shared genomic features of HIV+ diffuse large B-cell lymphoma in two African cohortsSophia M. Roush0Mishalan Moodley1Jenny Coelho2Samantha Beck3Amon Chirwa4Edwards Kasonkanji5Marriam Mponda6Maurice Mulenga7Tamiwe Tomoka8Hanri van Zijl9Katherine Hodkinson10Arshad Ismail11Senzo Mtshali12Jonathan Featherston13Satish Gopal14Matthew S. Painschab15Jenifer Vaughan16Yuri Fedoriw17Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina (UNC)Sequencing Core Facility, Division of the National Health Laboratory Service, National Institute for Communicable DiseasesDepartment of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina (UNC)Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina (UNC)UNC Project MalawiUNC Project MalawiUNC Project MalawiUNC Project MalawiUNC Project MalawiDepartment of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the WitwatersrandDepartment of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the WitwatersrandSequencing Core Facility, Division of the National Health Laboratory Service, National Institute for Communicable DiseasesSequencing Core Facility, Division of the National Health Laboratory Service, National Institute for Communicable DiseasesSequencing Core Facility, Division of the National Health Laboratory Service, National Institute for Communicable DiseasesNational Cancer Institute Center for Global HealthUNC Lineberger Comprehensive Cancer CenterDepartment of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the WitwatersrandDepartment of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina (UNC)Abstract The number of people with HIV (PWH) in Africa is rising due to population growth and antiretroviral therapy (ART) availability, with diffuse large B-cell lymphoma (DLBCL) a major cause of mortality. HIV and ART alter DLBCL tumor biology, but few studies of DLBCL include PWH or African patients, limiting translation of emerging treatment strategies. Here, we performed whole exome sequencing of 48 tumors (40 HIV-positive [HIV+]) with paired germline of DLBCL patients from Malawi and South Africa. HIV + DLBCL tumors had distinct mutations depending on ART exposure, and there were several recurrent deleterious variants, with ANKRD11 mutations being prognostic. One tumor from each cohort had high tumor mutational burden and microsatellite-instability with PMS2 and ARID1A mutation. These findings suggest shared genomic characteristics among HIV + DLBCL in Africa, offering opportunities for tailored biomarkers and therapeutic targets for this underserved population.https://doi.org/10.1038/s41598-025-10529-6
spellingShingle Sophia M. Roush
Mishalan Moodley
Jenny Coelho
Samantha Beck
Amon Chirwa
Edwards Kasonkanji
Marriam Mponda
Maurice Mulenga
Tamiwe Tomoka
Hanri van Zijl
Katherine Hodkinson
Arshad Ismail
Senzo Mtshali
Jonathan Featherston
Satish Gopal
Matthew S. Painschab
Jenifer Vaughan
Yuri Fedoriw
Shared genomic features of HIV+ diffuse large B-cell lymphoma in two African cohorts
Scientific Reports
title Shared genomic features of HIV+ diffuse large B-cell lymphoma in two African cohorts
title_full Shared genomic features of HIV+ diffuse large B-cell lymphoma in two African cohorts
title_fullStr Shared genomic features of HIV+ diffuse large B-cell lymphoma in two African cohorts
title_full_unstemmed Shared genomic features of HIV+ diffuse large B-cell lymphoma in two African cohorts
title_short Shared genomic features of HIV+ diffuse large B-cell lymphoma in two African cohorts
title_sort shared genomic features of hiv diffuse large b cell lymphoma in two african cohorts
url https://doi.org/10.1038/s41598-025-10529-6
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