| First Author | Feng X | Year | 2020 |
| Journal | DNA Repair (Amst) | Volume | 86 |
| Pages | 102754 | PubMed ID | 31794893 |
| Mgi Jnum | J:297725 | Mgi Id | MGI:6479181 |
| Doi | 10.1016/j.dnarep.2019.102754 | Citation | Feng X, et al. (2020) Loss of Setd4 delays radiation-induced thymic lymphoma in mice. DNA Repair (Amst) 86:102754 |
| abstractText | Radiation-induced lymphomagenesis results from a clonogenic lymphoid cell proliferation due to genetic alterations and immunological dysregulation. Mouse models had been successfully used to identify risk and protective factors for radiation-induced DNA damage and carcinogenesis. The mammalian SETD4 is a poorly understood putative methyl-transferase. Here, we report that conditional Setd4 deletion in adult mice significantly extended the survival of radiation-induced T-lymphoma. However, in Tp53 deficient mice, Setd4 deletion did not delay the radiation-induced lymphomagenesis although it accelerated the spontaneous T-lymphomagenesis in non-irradiated mice. The T-lymphomas were largely clonogenic in both Setd4(flox/flox) and Setd4(Delta/Delta) mice based on sequencing analysis of the T-cell antigen beta receptors. However, the Setd4(Delta/Delta) T-lymphomas were CD4(+)/CD8(+) double positive, while the littermate Setd4(flox/flox)tumor were largely CD8+ single positive. A genomic sequencing analysis on chromosome deletion, inversion, duplication, and translocation, revealed a larger contribution of inversion but a less contribution of deletion to the overall chromosome rearrangements in the in Setd4(Delta/Delta) tumors than the Setd4(flox/flox) tumors. In addition, the Setd4(flox/flox) mice died more often from the large sizes of primary thymus lymphoma at earlier time, but there was a slight increase of lymphoma dissemination among peripheral organs in Setd4(Delta/Delta) at later times. These results suggest that Setd4 has a critical role in modulating lymphomagenesis and may be targeted to suppress radiation-induced carcinogenesis. |
