| First Author | Bianchi JJ | Year | 2019 |
| Journal | Cell Rep | Volume | 27 |
| Issue | 10 | Pages | 2847-2858.e4 |
| PubMed ID | 31167132 | Mgi Jnum | J:280097 |
| Mgi Id | MGI:6358961 | Doi | 10.1016/j.celrep.2019.05.014 |
| Citation | Bianchi JJ, et al. (2019) Breakage-Fusion-Bridge Events Trigger Complex Genome Rearrangements and Amplifications in Developmentally Arrested T Cell Lymphomas. Cell Rep 27(10):2847-2858.e4 |
| abstractText | To reveal the relative contribution of the recombination activating gene (RAG)1/2 nuclease to lymphomagenesis, we conducted a genome-wide analysis of T cell lymphomas from p53-deficient mice expressing or lacking RAG2. We found that while p53(-/-) lymphoblastic T cells harbor primarily ectopic DNA deletions, Rag2(-/-)p53(-/-) T cell lymphomas display complex genomic rearrangements associated with amplification of the chromosomal location 9qA4-5.3. We show that this amplicon is generated by breakage-fusion-bridge during mitosis and arises distinctly in T cell lymphomas originating from an early progenitor stage. Notably, we report amplification of the corresponding syntenic region (11q23) in a subset of human leukemia leading to the overexpression of several cancer genes, including MLL/KMT2A. Our findings provide direct evidence that lymphocytes undergo malignant transformation through distinct genome architectural routes that are determined by both RAG-dependent and RAG-independent DNA damage and a block in cell development. |
