Deficiency in the DNA glycosylases UNG1 and OGG1 does not potentiate c-Myc-induced B-cell lymphomagenesis.

C-Myc overexpression mediates lymphomagenesis; however, secondary genetic lesions are required for its full oncogenic potential. The origin and the mechanism of formation of these mutations are unclear. Using the lacI mutation detection system, we show that secondary mutations occur early in B-cell development and are repaired by Msh2. The mutations at the lacI gene were predominantly at C:G base pairs and CpG motifs, suggesting that they were formed due to cytosine deamination or oxidative damage of G. Therefore, we investigated the role of Ogg1 and UNG glycosylases in c-Myc-driven lymphomagenesis but found that their deficiencies did not influence disease outcome in the Eµ c-Myc mouse model. We also show that Rag proteins do not contribute to secondary lesions in this model. Our work suggests that mutations at C:G base pairs that are repaired primarily by the mismatch repair system arise early in B-cell ontogeny to promote c-Myc-driven lymphomagenesis.