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<p>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 <i>ANKRD11</i> mutations being prognostic. One tumor from each cohort had high tumor mutational burden and microsatellite-instability with <i>PMS2</i> and <i>ARID1A</i> mutation. These findings suggest shared genomic characteristics among HIV + DLBCL in Africa, offering opportunities for tailored biomarkers and therapeutic targets for this underserved population.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月9日

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  • 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

摘要

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.