Mosaic chromosomal alterations detected in men living with HIV and the relationship to non-Hodgkin lymphoma
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7 01 2023
Source: AIDS. 37(8):1307-1313
Details:
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Alternative Title:AIDS
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Personal Author:
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Description:Objectives:
People living with HIV (PLWH) have elevated risk of non-Hodgkin lymphoma (NHL) and other diseases. Studying clonal hematopoiesis (CH), the clonal expansion of mutated hematopoietic stem cells, could provide insights regarding elevated NHL risk.
Design:
Cohort analysis of participants in the Multicenter AIDS Cohort Study (N=5,979).
Methods:
Mosaic chromosomal alterations (mCAs), a type of CH, were detected from genotyping array data using MoChA. We compared CH prevalence in men living with HIV (MLWH) to HIV-uninfected men using logistic regression, and among MLWH, assessed the associations of CH with NHL incidence and overall mortality using Poisson regression.
Results:
Comparing MLWH to HIV-uninfected men, we observed no difference in the frequency of autosomal mCAs (3.9% vs. 3.6%, p-value=0.09) or mosaic loss of the Y chromosome (mLOY) (1.4% vs. 2.9%, p-value=0.13). Autosomal mCAs involving copy-neutral loss of heterozygosity (CN-LOH) of chromosome 14q were more common in MLWH. Among MLWH, mCAs were not associated with subsequent NHL incidence (autosomal mCA p-value=0.65, mLOY p-value=0.48). However, two MLWH with diffuse large B-cell lymphoma had overlapping CN-LOH mCAs on chromosome 19 spanning U2AF2 (involved in RNA splicing), and one MLWH with Burkitt lymphoma had high-frequency mCAs involving chromosome 1 gain and chromosome 17 CN-LOH (cell fractions 22.1% and 25.0%, respectively). mCAs were not associated with mortality among MLWH (autosomal mCA p-value=0.52, mLOY p-value=0.93).
Conclusions:
We found limited evidence for a relationship between HIV infection and mCAs. Although mCAs were not significantly associated with NHL, mCAs detected in several NHL cases indicate a need for further investigation.
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Source:
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Pubmed ID:36927626
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Pubmed Central ID:PMC10500031
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Supporting Files:No Additional Files
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