Epigenomic evolution in diffuse large B-cell lymphomas Academic Article uri icon


MeSH Major

  • Biological Evolution
  • Epigenomics
  • Lymphoma, Large B-Cell, Diffuse


  • The contribution of epigenomic alterations to tumour progression and relapse is not well characterized. Here we characterize an association between disease progression and DNA methylation in diffuse large B-cell lymphoma (DLBCL). By profiling genome-wide DNA methylation at single-base pair resolution in thirteen DLBCL diagnosis-relapse sample pairs, we show that DLBCL patients exhibit heterogeneous evolution of tumour methylomes during relapse. We identify differentially methylated regulatory elements and determine a relapse-associated methylation signature converging on key pathways such as transforming growth factor-β (TGF-β) receptor activity. We also observe decreased intra-tumour methylation heterogeneity from diagnosis to relapsed tumour samples. Relapse-free patients display lower intra-tumour methylation heterogeneity at diagnosis compared with relapsed patients in an independent validation cohort. Furthermore, intra-tumour methylation heterogeneity is predictive of time to relapse. Therefore, we propose that epigenomic heterogeneity may support or drive the relapse phenotype and can be used to predict DLBCL relapse.

publication date

  • April 22, 2015



  • Academic Article



  • eng

PubMed Central ID

  • PMC4411286

Digital Object Identifier (DOI)

  • 10.1038/ncomms7921

PubMed ID

  • 25891015

Additional Document Info

start page

  • 6921


  • 6