Critical role for Atm in suppressing V(D)J recombination-driven thymic lymphoma

被引:89
作者
Liao, MJ [1 ]
Van Dyke, T [1 ]
机构
[1] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Sch Med, Chapel Hill, NC 27599 USA
关键词
Atm; V(D)J recombination; lymphoma; tumor suppression;
D O I
10.1101/gad.13.10.1246
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Chromosome translocations involving T cell receptor (TCR) loci have been found in tumors from Ataxia telangiectasia (AT) patients and in mouse Atm(-/-) thymoma, suggesting the involvement of V(D)J recombination in these malignancies. By introducing a RAG-1 deficiency into Atm(-/-) mice in the presence of a TCR transgene, rye show that V(D)J recombination is critical for thymoma development in these mice. Therefore, aberrant V(D)J recombination, normally suppressed by Atm, facilitates tumorigenic events leading to cancer. Because V(D)J recombination is dispensable for lymphomagenesis upon p53 deficiency, this study also indicates that Atm and p53 function by distinct mechanisms in suppressing thymoma.
引用
收藏
页码:1246 / 1250
页数:5
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