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@ARTICLE{Glaser:300295,
      author       = {S. Glaser and R. Wagener and H. Kretzmer and C. López and
                      M. J. Baptista and S. Bens and S. Bernhart and K. Bhatia and
                      A. Borkhardt and S. Elgaafary and S. Hoffmann and D.
                      Hübschmann and M. Hummel and W. Klapper and J. Kolarova and
                      M. Kreuz and S. Lazzi and M. Löffler and J. T. Navarro and
                      J. Neequaye and N. Onyango and T. Onyuma and G. Ott and B.
                      Radlwimmer$^*$ and M. Rohde and A. Rosenwald and M.
                      Rosolowski and M. Schlesner and M. Szczepanowski and G.
                      Tapia and W. Wößmann and R. Küppers$^*$ and L. Trümper
                      and L. Leoncini and P. Lichter$^*$ and C. Del Val and O.
                      Ammerpohl and B. Burkhardt and S. M. Mbulaiteye and R.
                      Siebert and I. M. Consortium},
      collaboration = {M. Project},
      title        = {{S}ubtyping {B}urkitt {L}ymphoma by {DNA} {M}ethylation.},
      journal      = {Genes, chromosomes $\&$ cancer},
      volume       = {64},
      number       = {4},
      issn         = {1045-2257},
      address      = {New York, NY},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2025-00748},
      pages        = {e70042},
      year         = {2025},
      abstract     = {Burkitt lymphoma (BL) is an aggressive germinal center
                      B-cell-derived malignancy. Historically, sporadic, endemic,
                      and immunodeficiency-associated variants were distinguished,
                      which differ in the frequency of Epstein-Barr virus (EBV)
                      positivity. Aiming to identify subgroups based on DNA
                      methylation patterns, we here profiled 96 BL cases, 17 BL
                      cell lines, and six EBV-transformed lymphoblastoid cell
                      lines using Illumina BeadChip arrays. DNA methylation
                      analyses clustered the cases into four subgroups: two
                      containing mostly EBV-positive cases (BL-mC1, BL-mC2) and
                      two containing mostly EBV-negative cases (BL-mC3, BL-mC4).
                      The subgroups BL-mC1/2, enriched for EBV-positive cases,
                      showed increased DNA methylation, epigenetic age, and, in
                      part, proliferation history compared to BL-mC3/4. CpGs
                      hypermethylated in EBV-positive BLs were enriched for
                      polycomb repressive complex 2 marks, while the CpGs
                      hypomethylated in EBV-negative BLs were linked to, for
                      example, B-cell receptor signaling. EBV-associated
                      hypermethylation affected regulatory regions of genes
                      frequently mutated in BL (e.g., CCND3, TP53) and impacted
                      superenhancers. This finding suggests that hypermethylation
                      may compensate for the lower mutational burden of pathogenic
                      drivers in EBV-positive BLs. Though minor, significant
                      differences were also observed between EBV-positive endemic
                      and sporadic cases (e.g., at the SOX11 and RUNX1 loci). Our
                      findings suggest that EBV status, rather than
                      epidemiological variants, drives the DNA methylation-based
                      subgrouping of BL.},
      keywords     = {Humans / Burkitt Lymphoma: genetics / Burkitt Lymphoma:
                      classification / Burkitt Lymphoma: virology / Burkitt
                      Lymphoma: pathology / DNA Methylation / Herpesvirus 4,
                      Human: genetics / Epstein-Barr Virus Infections: genetics /
                      Epstein-Barr Virus Infections: virology / Female / CpG
                      Islands / Male / Child / Cell Line, Tumor / Adult /
                      Epigenesis, Genetic / Child, Preschool / Middle Aged /
                      Adolescent / Africa (Other) / Burkitt lymphoma (Other) / DNA
                      methylation (Other) / Epstein–Barr virus (Other) /
                      immunodeficiency (Other)},
      cin          = {B060 / ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)B060-20160331 / I:(DE-He78)ED01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40192513},
      pmc          = {pmc:PMC11974478},
      doi          = {10.1002/gcc.70042},
      url          = {https://inrepo02.dkfz.de/record/300295},
}