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

作者：Kang Yun Hee; Son Chae Yeon; Lee Chul Ho; Ryu Chun Jeih^*

来源：Oncology Reports, 2010, 23(5): 1463-1468.

DOI：10.3892/or_00000785

• TCR beta gene enhancer
• E beta-independent V(D)J cleavages
• aberrant cleavages
• lymphoma cells
• cryptic recombination signal sequences

Previously, we generated thymic lymphoma cell lines from E beta(R/R)p53(-/-) (EP) double mutant mice where the T cell receptor (TCR) beta enhancer (E beta) was deleted, and the p53 gene was inactivated. Here, we characterized the EP cell lines to study the roles of the E beta and p53 on TCR beta rearrangements during lymphomagenesis. Recombination activation genes (RAGs) were expressed. while the TCR beta chain was not expressed in the EP cell lines. D beta-J beta rearrangements were not detected at all, and D beta 1 and D beta 2 cleavages were also not detected in the EP cell lines. However. J beta cleavages suppressed in E beta mutant thymocytes were readily detected in the EP cell lines. The J beta cleavages appeared to be uncoupled, aberrant, RAG-dependent and E beta-independent and were not detected in a p53 or E beta single mutant background, suggesting that the J beta cleavages are selected in the E beta and p53 double mutant background. Sequence analysis showed that the cleavage occurred in the cryptic recombination signal sequences (RSSs) present throughout J beta 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.

• 出版日期2010-5