Critical role for Atm in suppressing V(D)J recombination-driven thymic lymphoma.
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.
Liao
M J
MJ
Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina (UNC) at Chapel Hill, North Carolina 27599-3280 USA.
Van Dyke
T
T
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics*; D019674:Genes, T-Cell Receptor beta; D016158:Genes, p53 / Q000502:physiology; D018398:Homeodomain Proteins / Q000502:physiology; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000502:physiology*; D013945:Thymoma / Q000235:genetics*; D013953:Thymus Neoplasms / Q000235:genetics*; D013997:Time Factors; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; C064658:RAG-1 protein; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases