2026-07-23T17:12:28Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/132482024-09-27T08:02:38Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607

00925njm 22002777a 4500 dc Delgado, Pilar author Alvarez-Prado, Angel Francisco author Marina-Zarate, Ester author Sernandez, Isora V. author Mur, Sonia M. author de la Barrera, Jorge author Sanchez-Cabo, Fatima author Cañamero, Marta author Molina-Iracheta, Antonio author Belver, Laura author de Yebenes, Virginia G author Ramiro, Almudena R author 2020-12 Most B cell lymphomas originate from B cells that have germinal center (GC) experience and bear chromosome translocations and numerous point mutations. GC B cells remodel their immunoglobulin (Ig) genes by somatic hypermutation (SHM) and class switch recombination (CSR) in their Ig genes. Activation Induced Deaminase (AID) initiates CSR and SHM by generating U:G mismatches on Ig DNA that can then be processed by Uracyl-N-glycosylase (UNG). AID promotes collateral damage in the form of chromosome translocations and off-target SHM, however, the exact contribution of AID activity to lymphoma generation and progression is not completely understood. Here we show using a conditional knock-in strategy that AID supra-activity alone is not sufficient to generate B cell transformation. In contrast, in the absence of UNG, AID supra-expression increases SHM and promotes lymphoma. Whole exome sequencing revealed that AID heavily contributes to lymphoma SHM, promoting subclonal variability and a wider range of oncogenic variants. Thus, our data provide direct evidence that UNG is a brake to AID-induced intratumoral heterogeneity and evolution of B cell lymphoma. PLoS Genet. 2020; 16(12):e1008960 10.1371/journal.pgen.1008960 1553-7404 PLoS genetics 33362210 http://hdl.handle.net/20.500.12105/13248 Interplay between UNG and AID governs intratumoral heterogeneity in mature B cell lymphoma.