A comprehensive modular map of Diffuse Large B-cell Lymphoma

Abstract

AbstractDiffuse large B-cell lymphoma (DLBCL) is characterised by pronounced genetic and biological heterogeneity. Several partially overlapping classification systems exist – developed from mutation, rearrangement or gene expression data from single studies. We apply a customised network analysis to nearly five thousand DLBCL cases to identify and quantify modules of tumour biology. Shared patterns of activity in these tumour biology modules identify biologically similar DLBCL, which resolve into communities of related cases. These lymphoma communities correlate with genetic mutation and rearrangement status, supporting and extending existing concepts of disease biology and delivering insight into relationships between differentiation state, genetic subtypes and rearrangement status. A notable example are communities linked to distinct germinal centre states that separate DLBCL respectively associated withMYC/BCL2andMYC/BCL6double hit rearrangement. By exploiting network analysis across a large number of well characterised cases, this study provides the first birds eye view of DLBCL tumour biology.