TitleEpigenomic evolution in diffuse large B-cell lymphomas.
Publication TypeJournal Article
Year of Publication2015
AuthorsPan, Heng, Jiang Yanwen, Boi Michela, Tabbò Fabrizio, Redmond David, Nie Kui, Ladetto Marco, Chiappella Annalisa, Cerchietti Leandro, Shaknovich Rita, Melnick Ari M., Inghirami Giorgio G., Tam Wayne, and Elemento Olivier
JournalNat Commun
Volume6
Pagination6921
Date Published2015 Apr 20
ISSN2041-1723
KeywordsBiological Evolution, DNA Methylation, Epigenomics, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Humans, Lymphoma, Large B-Cell, Diffuse, Neoplasm Proteins, Recurrence, Transcriptome
Abstract

<p>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.</p>

DOI10.1038/ncomms7921
Alternate JournalNat Commun
PubMed ID25891015
PubMed Central IDPMC4411286