Molecular characterization of the t(10;14) translocation breakpoints in T-cell acute lymphoblastic leukemia: further evidence for illegitimate physiological recombination.

The t(10;14)(q24;q11) translocation is a non-random chromosome change seen in the leukemic cells of 5-10% of patients with T-cell acute lymphoblastic leukemia (T-ALL). Recent studies support the hypothesis that the translocation occurs in the course of aberrant physiological recombination and results in the juxtaposition of a T-cell receptor (TCR) gene in 14q11 with a putative oncogene, TCL3, in 10q24. We cloned and sequenced the translocation breakpoints on both derivative 10q+ and 14q- chromosomes from a patient with t(10;14)(q24;q11) T-ALL. Two distinct diversity segments of TCRD, D delta 2 and D delta 3, were identified at the two translocation breakpoints on chromosome 14. The 9.5 kb DNA that separates these two subunits in the germline was deleted, possibly in the course of a D-D joining event. The two chromosome 10 breakpoints were 10 nucleotides apart and occurred in the immediate vicinity of a pseudo-heptamer signal motif. N-region addition is also evident at the breakpoint on the derivative chromosome 10. Our observations strongly suggest that the IG/TCR recombinase normally involved in V-(D)-J joining was involved in the process of the t(10;14)(q24;q11) translocation.