Disruption of epigenetic regulation of enhancers in the germinal center reaction drives clonal evolution in Follicular Lymphoma

点击翻译按钮获取中文摘要

PROJECT SUMMARY/ABSTRACT Follicular Lymphoma (FL) is the second most common form of non-Hodgkin's lymphoma, accounting for 20- 30% of non-Hodgkin's lymphoma diagnoses. Though FL is an indolent disease, it eventually transforms into more aggressive, incurable forms of lymphoma. FL is hallmarked by the anti-apoptotic IGH/BCL2 translocation, which is often accompanied by a mutation in an epigenetic gene. Here, we propose to investigate the roles of these mutations in epigenetic genes, specifically KMT2D and CREBBP due to their high rate of occurrence, in the development and transformation process of FL. In our first aim, we plan to use mixed bone marrow chimera mouse models to determine the role of these mutations in driving early clonal evolution of the disease. In our second aim, we plan to then characterize the gene expression and chromatin accessibility of the resulting lymphoma to determine how these mutations cooperate to drive progression through epigenetic reprogramming of the tumor.