Comparison of the Mutational Profile between BCL2- and BCL6-Rearrangement Positive Follicular Lymphoma

Abstract

It was recently reported that follicular lymphoma (FL) with BCL6 rearrangement (R) is associated with favorable progression-free survival, whereas BCL2-R and BCL2-6-R cases are associated with disease progression. However, the pathologic mechanism remained unexplored. This study analyzed the mutational landscape and immune microenvironment of 31 FL cases, including 16 BCL2-R, 11 BCL6-R, and 4 BCL2-6-R FL cases. The method included an in-house next-generation targeted sequencing panel of 168 genes associated with aggressive B-cell lymphoma and FL, whole genome copy number change microarray (OncoScan), and immunohistochemistry for the immune microenvironment focused on M2-like tumor-associated macrophages, regulatory T lymphocytes, and programmed cell death protein 1 (PDCD1; alias PD-1)-positive follicular T helper cells. The resulting mutational profile was compatible with a previously reported conventional FL series featuring frequent mutations in CREBBP, KMT2D, TNFRSF14, STAT6, and CD36. Moreover, BCL6-R cases had mutations in ARID1B, ARID5B, and RHOA; low frequency of mutations in other genes, such as OSBPL10, PTPRD, ATM, and HLA-B; 6q loss; and absence of disease progression. In comparison with BCL6-R cases, BCL2-R and BCL2-6-R cases had mutations in EZH2, chromosome 18 copy number gain, and disease progression in some cases. The immune microenvironment profile was heterogeneous; however, BCL6-R cases demonstrated higher infiltration of colony-stimulating factor 1 receptor- and leukocyte immunoglobulin like receptor B3 (LILRB3; alias CD85a)-positive cells. In conclusion, compared with BCL2-R, FL with BCL6-R exhibited some differences in mutational profiles and immune microenvironment.