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Journal articles
Breakage-Fusion-Bridge Events Trigger Complex Genome Rearrangements and Amplifications in Developmentally Arrested T Cell Lymphomas
Abstract : 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.
Cited literature [103 references]
https://hal-pasteur.archives-ouvertes.fr/pasteur-02757480
Contributor : Chloé Lescale Connect in order to contact the contributor
Submitted on : Thursday, June 4, 2020 - 12:31:08 AM
Last modification on : Tuesday, January 11, 2022 - 1:02:01 PM
Contributor : Chloé Lescale Connect in order to contact the contributor
Submitted on : Thursday, June 4, 2020 - 12:31:08 AM
Last modification on : Tuesday, January 11, 2022 - 1:02:01 PM
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