Block of T cell development in P53-deficient mice accelerates development of lymphomas with characteristic RAG-dependent cytogenetic alterations

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Title
Block of T cell development in P53-deficient mice accelerates development of lymphomas with characteristic RAG-dependent cytogenetic alterations
Author(s)
B B Haines; Chun Jeih Ryu; S Chang; A Protopopov; A Luch; Yun Hee Kang; D D Draganov; M F Fragoso; S G Paik; Hyo Jeong Hong; R A DePinho; J Chen
Bibliographic Citation
Cancer Cell, vol. 9, no. 2, pp. 109-120
Publication Year
2006
Abstract
Mice deficient in the DNA damage sensor P53 display normal T cell development but eventually succumb to thymic lymphomas. Here, we show that inactivation of the TCR β gene enhancer (Eβ) results in a block of T cell development at stages where recombination-activating genes (RAG) are expressed. Introduction of the Eβ mutation into p53-/- mice dramatically accelerates the onset of lethal thymic lymphomas that harbor RAG-dependent aberrant rearrangements, chromosome 14 and 12 translocations, and amplification of the chromosomal region 9A1-A5.3. Phenotypic and genetic analyses suggest that lymphomas emerge through a normal thymocyte development pathway. These findings provide genetic evidence that block of lymphocyte development at stages with RAG endonuclease activity can provoke lymphomagenesis on a background with deficient DNA damage responses.
ISSN
1535-6108
Publisher
Elsevier-Cell Press
DOI
http://dx.doi.org/10.1016/j.ccr.2006.01.004
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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