Mosaic chromosomal alterations detected in men living with HIV and the relationship to non-Hodgkin lymphoma

Details

• Alternative Title:
  AIDS
• Personal Author:
  LIN, Shu-Hong ; KHAN, Sairah M. ; ZHOU, Weiyin ; BROWN, Derek W. ; VERGARA, Candelaria ; WOLINSKY, Steven M. ; MARTÍNEZ-MAZA, Otoniel ; MARGOLICK, Joseph B. ; MARTINSON, Jeremy J. ; HUSSAIN, Shehnaz K. ; ENGELS, Eric A. ; MACHIELA, Mitchell J.
• 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.
  
  
• Subjects:
  Chromosomes, Human, Y Cohort Studies HIV Infections Humans Lymphoma, Non-Hodgkin Male Mosaicism
• Keywords:
  Chromosomal Alteration Clonal Hematopoiesis Genetic Mosaicism Human Immunodeficiency Virus Non-Hodgkin Lymphoma
• Source:
  AIDS. 37(8):1307-1313
• Pubmed ID:
  36927626
• Pubmed Central ID:
  PMC10500031
• Document Type:
  Journal Article
• Funding:
  U01 AI035042/AI/NIAID NIH HHSUnited States/ ; HHSN261201000140C/CA/NCI NIH HHSUnited States/ ; HHSN261201000035C/CA/NCI NIH HHSUnited States/ ; UL1 TR001079/TR/NCATS NIH HHSUnited States/ ; U01 AI035041/AI/NIAID NIH HHSUnited States/ ; UM1 AI035043/AI/NIAID NIH HHSUnited States/ ; U58 DP000795/DP/NCCDPHP CDC HHSUnited States/ ; Z99 CA999999/ImNIH/Intramural NIH HHSUnited States/ ; U01 HL146201/HL/NHLBI NIH HHSUnited States/ ; HHSN261201000035I/CA/NCI NIH HHSUnited States/ ; HHSN261201000034C/CA/NCI NIH HHSUnited States/ ; U58 DP003862/DP/NCCDPHP CDC HHSUnited States/ ; U01 AI035040/AI/NIAID NIH HHSUnited States/ ; U01 HL146240/HL/NHLBI NIH HHSUnited States/ ; U01 AI035039/AI/NIAID NIH HHSUnited States/
• Volume:
  37
• Issue:
  8
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:b981c5b25d408bfc9ffc51d22b25216bb51128b13382afae8e804132471b91710374db49522f20312b623ffa54036f47b8d9b054344a92916037449003f08ac3
• Download URL:
  https://stacks.cdc.gov/view/cdc/148846/cdc_148846_DS1.pdf
• File Type:
  [PDF - 659.42 KB ]