Epigenomic evolution in diffuse large B-cell lymphomas.

TitleEpigenomic evolution in diffuse large B-cell lymphomas.
Publication TypeJournal Article
Year of Publication2015
AuthorsPan H, Jiang Y, Boi M, Tabbò F, Redmond D, Nie K, Ladetto M, Chiappella A, Cerchietti L, Shaknovich R, Melnick AM, Inghirami GG, Tam W, Elemento O
JournalNat Commun
Date Published2015 Apr 20
KeywordsBiological Evolution, DNA Methylation, Epigenomics, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Humans, Lymphoma, Large B-Cell, Diffuse, Neoplasm Proteins, Recurrence, Transcriptome

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.

Alternate JournalNat Commun
PubMed ID25891015
PubMed Central IDPMC4411286