Investigating polyclonal Follicular Lymphoma tumors to determine the inciting factors for lymphomagenesis 4549

Abstract Description Follicular Lymphoma (FL) is a germinal center-derived malignancy representing approximately 20% of all non-Hodgkin’s lymphomas. Despite a relatively indolent disease course, FL is a biologically and clinically heterogeneous disease which poses significant clinical challenges due to its propensity for relapse and transformation into aggressive and untreatable forms of lymphoma. Here, we have leveraged computational techniques with WES, RNA-sequencing, and immune profiling data from FL tumors to gain further insight into the biologic basis for FL heterogeneity. We performed computational reconstruction of the B cell receptor repertoire on B cell sorted RNA-sequencing data from normal lymph nodes (n = 5) and FL tumors (n = 89). To gain a better understanding of FL B cell biology at the single cell level, we further investigated the clonal architecture of dominant malignant clonotypes in FL tumors using computational analysis of paired single cell V(D)J and 5’ GEX sequencing data from FL tumors (n = 21) and non-malignant lymph nodes (n = 3), allowing us to characterize the germinal center programs in malignant versus non-malignant B cells. Our data suggest that a subset of FL tumors consist of complex polyclonal B cell populations, some of which represent a pre-malignant FL precursor. Our data provide a deepened understanding of FL biology, including precursor cells, and contributes a refined transcriptomic characterization of malignant and non-malignant B cells in Follicular Lymphoma. Funding Sources This work was supported by the National Institutes of Health (R01 CA212162-01A1 to A.J.N and J.R.C., and P50 CA097274 to J.R.C., and A.J.N) Topic Categories Computational and Systems Immunology (COMP)