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

Abstract
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, we 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.

Publication details
Download http://www.pubmedcentral.gov/articlerender.fcgi?artid=316723
Publisher Cold Spring Harbor Laboratory Press
Repository PubMed Central (PMC3 - NLM DTD) (United States)
Keywords Research Communication
Type Text
Language Englisch