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Title 

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

Authors 

B B HainesChun Jeih RyuS ChangA ProtopopovA LuchYun Hee KangD D DraganovM F FragosoS G PaikHyo Jeong HongR A DePinhoJ Chen

Publisher 

Elsevier (Cell Press)

Issue Date 

2006

Citation 

Cancer Cell, vol. 9, no. 2, pp. 109-120

Keywords 

protein p53T lymphocyte receptor beta chainanimal cellanimal experimentcell maturationchromosome aberrationchromosome translocationcontrolled studycytogeneticsdevelopmental stage

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

Link 

http://dx.doi.org/10.1016/j.ccr.2006.01.004

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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