Diffuse 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 with MYC/BCL2 and MYC/BCL6 double 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.

The authors have declared no competing interest.

This work was supported by Cancer Research UK program grant (C7845/A17723 and C7845/A29212) (M.C, G.D., D.W, and R.T). HMRN is supported by Cancer Research UK program grant A29685 (D.P., S.C., A.S., E.R.). D.J.H was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. D.J.H. was supported by a fellowship from Cancer Research UK (CRUK) (RCCFEL∖100072) and received core funding from Wellcome (203151/Z/16/Z) to the Wellcome-MRC Cambridge Stem Cell Institute and from the CRUK Cambridge Centre (A25117).

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https://www.ncbi.nlm.nih.gov/geo/ GSE4475, GSE4732, GSE10846,GSE12195,GSE19246_FF,GSE22470,GSE31312,GSE32918,GSE34171,GSE53786,GSE87371,GSE9858,GSE181063,GSE117566 PubMedID15550490 PudMedID29641966(NCICCR-DLBCL) https://ega-archive.org/ EGAS00001002606)

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