title: Mutation of chromatin modifiers; an emerging hallmark of germinal center B-cell lymphomas.
abstract: Subtypes of non-Hodgkin's lymphomas align with different stages of B-cell development. Germinal center B-cell (GCB)-like diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Burkitt's lymphoma (BL) each share molecular similarities with normal GCB cells. Recent next-generation sequencing studies have gained insight into the genetic etiology of these malignancies and revealed a high frequency of mutations within genes encoding proteins that modifying chromatin. These include activating and inactivating mutations of genes that perform post-translational modification of histones and organize chromatin structure. Here, we discuss the function of histone acetyltransferases (CREBBP, EP300), histone methyltransferases (KDM2C/D, EZH2) and regulators of higher order chromatin structure (HIST1H1C/D/E, ARID1A and SMARCA4) that have been reported to be mutated in ⩾5% of DLBCL, FL or BL. Mutations of these genes are an emerging hallmark of lymphomas with GCB-cell origins, and likely represent the next generation of therapeutic targets for these malignancies.
authors.affiliation: Lymphoma Precision Medicine Laboratory, Dr James O Armitage Center for Leukemia and Lymphoma Research, University of Nebraska Medical Center, Omaha, NE, USA.|Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Lunning
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.|Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Green
mesh_terms: D000818:Animals; D002843:Chromatin; D018858:Germinal Center / Q000473:pathology; D051548:Histone Acetyltransferases / Q000235:genetics*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*
chemical_list: D002843:Chromatin; D009687:Nuclear Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D051548:Histone Acetyltransferases