Abstract 555: DNA methylation patterns are associated with subpopulations of diffuse large B-cell lymphoma

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Diffuse large B-cell lymphoma (DLBCL) comprises two predominant molecular subtypes: germinal-center B-cell-like (GCB) and activated B-cell-like (ABC). These subtypes were initially identified by their gene expression profiles, which are reminiscent of the cell of origin of the lymphoma. Though histologically indistinguishable, these subtypes are associated with distinct clinical outcomes and may be predictive for response to novel therapies. The development of improved diagnostic biomarkers for these DLBCL subtypes could therefore inform clinical decision-making by enabling selection of patients likely to respond to such novel therapies. To investigate regulatory mechanisms potentially responsible for the differential gene expression patterns seen in the DLBCL subtypes and to identify potential biomarkers for these subtypes, we performed whole genome methylation profiling of 15 DLBCL cell lines and 21 DLBCL patient tissues and identified distinct DNA methylation patterns associated with the two DLBCL molecular subtypes. Analysis of the methylation patterns of several DLBCL classifier genes known to be differentially expressed in ABC compared to GCB revealed the classic DNA methylation correlation pattern: high mRNA expression was associated with low methylation in the vicinity of the transcriptional start site (TSS), and vice versa. Furthermore, comparison of differential methylation profiles with corresponding RNA-seq data further supports the notion that DNA methylation profiles underlie the gene expression patterns that are currently used to classify ABC and GCB DLBCL subtypes. Collectively, these data suggest that DNA methylation may contribute to the regulation of expression of key ABC and GCB DLBCL classifier genes and further, that the DNA methylation state at these loci could potentially serve as useful diagnostic biomarkers for the DLBCL subtypes. Citation Format: Jenny Wu, Ron McCord, Thomas Sandmann, Kim Walter, Richard Bourgon, Robert Soriano, Zora Modrusan, Walter Darbonne, Kirsten E. Mundt. DNA methylation patterns are associated with subpopulations of diffuse large B-cell lymphoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 555. doi:10.1158/1538-7445.AM2014-555