| First Author | Delgado P | Year | 2020 |
| Journal | PLoS Genet | Volume | 16 |
| Issue | 12 | Pages | e1008960 |
| PubMed ID | 33362210 | Mgi Jnum | J:300808 |
| Mgi Id | MGI:6503915 | Doi | 10.1371/journal.pgen.1008960 |
| Citation | Delgado P, et al. (2020) Interplay between UNG and AID governs intratumoral heterogeneity in mature B cell lymphoma. PLoS Genet 16(12):e1008960 |
| abstractText | 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. |
