Fig. 4
From: Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma
Somatic and germline events affecting the Fcγ receptor locus. a The genes in the locus are shown with the recent duplication delineated in yellow and blue. Binned read depth from tumours is summarised using vertical bars. Germline CNVs, such as the gain and deletion shown in orange, are common in this region but can be readily distinguished from somatic events in paired analyses. In pink are four examples of somatic FCGR2B amplifications. FCRLA is completely or partially co-amplified in these. Blue arrows indicate breakpoints identified through visual inspection of data. Horizontal bars delineate the coordinates inferred to be contained within the amplified region. A break in the blue bar corresponding to approximately diploid coverage is indicative of the amplification affecting an allele representing the common deletion CNV. b In our validation cohort, we used custom ddPCR and targeted hybridisation capture to infer the presence of gains, deletions, and amplifications. Due to a lack of constitutional DNA for the validation cohort, we are unable to determine the proportion of single-copy gains and losses that can be attributed to common germline CNVs. The expression of each Fcγ receptor and FCRLA genes in the locus is shown with the cases separated by copy number state. Clustering on the expression of the four genes affected by amplifications groups amplified cases alongside some tumours with gains or no alteration detected, indicating the potential for additional avenues leading to FCGR2B over-expression. c Although rare overall, cases with the amplification showed a significantly shorter DSS and TTP (P = 0.012 and 0.044, respectively; log-rank test). d FCGR2B expression alone was also significantly associated with DSS and TTP within GCB cases. Specifically, stratifying on median expression or at any cut point above shows that GCB cases with higher FCGR2B exhibit significantly shorter TTP (P = 4.8 × 10−3, log-rank test), although DSS differences require a more stringent cutoff (see also Supplementary Figure 10)
