Block of T cell development in P53-deficient mice accelerates development of lymphomas with characteristic RAG-dependent cytogenetic alterations.
Cancer Cell
; 9(2): 109-20, 2006 Feb.
Article
in En
| MEDLINE
| ID: mdl-16473278
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 beta gene enhancer (E beta) results in a block of T cell development at stages where recombination-activating genes (RAG) are expressed. Introduction of the E beta 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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
Tumor Suppressor Protein p53
/
Chromosome Aberrations
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DNA-Binding Proteins
/
Lymphoma
Limits:
Animals
Language:
En
Journal:
Cancer Cell
Journal subject:
NEOPLASIAS
Year:
2006
Document type:
Article
Affiliation country:
United States
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA