The t(8; 14) chromosomal translocation occurring in B-cell malignancies results from mistakes in V–D–J joining

Publisher Website
Google Scholar
Abstract
The reciprocal chromosome translocation, t(8; 14), involving the heavy chain locus on chromosome 14 (refs 1, 2) and the c-myc oncogene on chromosome 8 (refs 3–5) is a characteristic of the B-cell malignancies Burkitt's lymphoma6 and acute lymphoblastic leukaemia (ALL)7. We have cloned and sequenced the t(8; 14) breakpoints of an African Burkitt's lymphoma cell line, P3HR–1, and a pre-B cell ALL cell line, 380 (ref. 8). In each case the region of chromosome 8 involved has recombined with a JH region on chromosome 14. The two sites of breakage on chromosome 8 lie within 70 base pairs (bp) of one another. At each joining site, sequences homologous to the signal sequences thought to be recognized by the V–D–J recombinase9 were identified, as were N regions9. In B-cell chronic lymphocytic leukaemias (B-CLL) carrying the t(11; 14) chromosome translocation10 and in follicular lymphomas carrying the t(14; 18) translocation11, the V–D–J recombinase is implicated in the mechanism of chromosomal translocations11. We speculate that the same enzymatic mechanism is responsible for the t(8; 14) translocations in African Burkitt's lymphoma and pre-B cell ALL.