SMARCA4 Confirmed as Tumor Suppressor in Germinal Center B Cell Lymphoma Mouse Models

A researcher trained at MD Anderson under M. Green and now at the Chinese Academy of Medical Sciences/CIMR presented work establishing SMARCA4 (BRG1), the shared ATPase of the SWI/SNF chromatin remodeling complex, as a tumor suppressor in germinal center-derived B cell lymphoma. In mouse conditional knockout models, heterozygous SMARCA4 loss skewed germinal centers toward the dark zone and expanded recycling centrocyte-to-centroblast cells, while homozygous loss sharply reduced germinal centers; in the Eμ-Myc lymphoma model, heterozygous loss shortened survival. The SWI/SNF inhibitor FHD-286 reduced tumor burden and extended survival in mutant tumors, with mechanistic work showing loss of accessibility at transcription factor motifs including IRF4, BCL6 and PAX5 targets.