The t(8; 14) chromosomal translocation occurring in B-cell malignancies results from mistakes in V-D-J joining.
The reciprocal chromosome translocation, t(8;14), involving the heavy chain locus on chromosome 14 and the c-myc oncogene on chromosome 8 is a characteristic of the B-cell malignancies Burkitt's lymphoma and acute lymphoblastic leukaemia (ALL). 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. 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 recombinase were identified, as were N regions. In B-cell chronic lymphocytic leukaemias (B-CLL) carrying the t(11; 14) chromosome translocation and in follicular lymphomas carrying the t(14; 18) translocation, the V-D-J recombinase is implicated in the mechanism of chromosomal translocations. 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.
D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics*; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D002898:Chromosomes, Human, Pair 8; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007945:Leukemia, Lymphoid / Q000235:genetics*; D011519:Proto-Oncogenes; D011995:Recombination, Genetic; D014178:Translocation, Genetic; D045567:VDJ Recombinases
D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases