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

Chromosome translocations involving T cell receptor (TCR) loci have been fo und in tumors from Ataxia telangiectasia (AT) patients and in mouse Atm(-/- ) thymoma, suggesting the involvement of V(D)J recombination in these malig nancies. By introducing a RAG-1 deficiency into Atm(-/-) mice in the presen ce of a TCR transgene, rye show that V(D)J recombination is critical for th ymoma development in these mice. Therefore, aberrant V(D)J recombination, n ormally suppressed by Atm, facilitates tumorigenic events leading to cancer . Because V(D)J recombination is dispensable for lymphomagenesis upon p53 d eficiency, this study also indicates that Atm and p53 function by distinct mechanisms in suppressing thymoma.