Identifying transcriptional profiles and evaluating prognostic biomarkers of HIV-associated diffuse large B-cell lymphoma from Malawi Public Deposited

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  • Fedoriw, Y.
    • Affiliation: University of North Carolina at Chapel Hill
  • Selitsky, S.
    • Affiliation: University of North Carolina at Chapel Hill
  • Montgomery, N.D.
    • Affiliation: University of North Carolina at Chapel Hill
  • Kendall, S.M.
    • Other Affiliation: Duke Cancer Institute and Center for Genomic and Computational Biology
  • Richards, K.L.
    • Other Affiliation: Cornell University
  • Du, W.
    • Other Affiliation: Cornell University
  • Tomoka, T.
    • Affiliation: School of Medicine, UNC Project-Malawi
  • Mulenga, M.
    • Other Affiliation: Kamuzu Central Hospital
  • Parker, J.S.
    • Affiliation: University of North Carolina at Chapel Hill
  • Dave, S.S.
    • Other Affiliation: Duke Cancer Institute and Center for Genomic and Computational Biology
  • Gopal, S.
    • Affiliation: School of Medicine, UNC Project-Malawi
Abstract
  • Lymphoma incidence in sub-Saharan Africa (SSA) is increasing due to HIV and population aging. Diffuse Large B-cell lymphoma (DLBCL), the most common lymphoma in SSA and worldwide, is highly associated with HIV, but molecular studies of HIV-associated DLBCL are scarce globally. We describe profiling of DLBCL from Malawi, aiming to elucidate tumor biology and identify clinically meaningful biomarkers specifically for SSA. Between June 1, 2013 and June 1, 2016, 59 cases of DLBCL (32 HIV+/27 HIV−) enrolled in the Kamuzu Central Hospital Lymphoma Study were characterized, of which 54 (92%) were negative for Epstein–Barr virus. Gene expression profiling (GEP) by whole transcriptome sequencing was performed on the first 36 cases (22 HIV+/14 HIV−). Immunohistochemistry (IHC) and GEP results were compared with published data and correlated to clinical outcome and pathologic features. Unsupervised clustering strongly segregated DLBCL by HIV status (p = 0.0003, Chi-squared test), indicating a marked contribution of HIV to expression phenotype. Pathway analysis identified that HIV-associated tumors were enriched in hypoxia, oxidative stress, and metabolism related gene expression patterns. Cell-of-origin subtype, determined by sequencing and IHC, did not associate with differences in overall survival (OS), while Ki-67 proliferation index ≥80% was associated with inferior OS in HIV+ DLBCL only (p = 0.03) and cMYC/BCL2 co-expression by IHC was negatively prognostic across the entire cohort (p = 0.01). This study provides among the first molecular characterizations of DLBCL from SSA, demonstrates marked gene expression differences by HIV status, and identifies genomic and immunophenotypic characteristics that can inform future basic and clinical investigations.
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  • Article
Rights statement
  • In Copyright
Journal title
  • Modern Pathology
Journal volume
  • 33
Journal issue
  • 8
Page start
  • 1482
Page end
  • 1491
ISSN
  • 0893-3952
Publisher
  • Springer Nature
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