Aberrant V(D)J cleavages in T cell receptor β enhancer- and p53-deficient lymphoma cells

Ryu
2010 Oncology Reports  
Previously, we generated thymic lymphoma cell lines from Eß R/R p53 -/-(EP) double mutant mice where the T cell receptor (TCR) ß enhancer (Eß) was deleted, and the p53 gene was inactivated. Here, we characterized the EP cell lines to study the roles of the Eß and p53 on TCRß rearrangements during lymphomagenesis. Recombination activation genes (RAGs) were expressed, while the TCRß chain was not expressed in the EP cell lines. Dß-Jß rearrangements were not detected at all, and Dß1 and Dß2
more » ... es were also not detected in the EP cell lines. However, Jß cleavages suppressed in Eß mutant thymocytes were readily detected in the EP cell lines. The Jß cleavages appeared to be uncoupled, aberrant, RAG-dependent and Eß-independent and were not detected in a p53 or Eß single mutant background, suggesting that the Jß cleavages are selected in the Eß and p53 double mutant background. Sequence analysis showed that the cleavage occurred in the cryptic recombination signal sequences (RSSs) present throughout Jß gene segments. The results implicate that the uncoupled and aberrant V(D)J cleavages may contribute to double-strand break-mediated genome instability during lymphomagenesis in EP mice.
doi:10.3892/or_00000785 fatcat:kzlqkux57zevtfpkzkozd5gw6a