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

Abstract

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.

• Authors: F G Haluska, S Finver, Y Tsujimoto, C M Croce
• Journal: Nature (Nature) 1986 Nov 13-19 Vol. 324 Issue 6093 Pg. 158-61 ISSN: 0028-0836 [Print] England
• PMID: 3097550 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA, Neoplasm
• Immunoglobulin Heavy Chains
• DNA Nucleotidyltransferases
• VDJ Recombinases

Topics

• Base Sequence
• Burkitt Lymphoma (genetics)
• Chromosome Mapping
• Chromosomes, Human, Pair 14
• Chromosomes, Human, Pair 8
• DNA Nucleotidyltransferases (metabolism)
• DNA, Neoplasm (genetics)
• Humans
• Immunoglobulin Heavy Chains (genetics)
• Leukemia, Lymphoid (genetics)
• Proto-Oncogenes
• Recombination, Genetic
• Translocation, Genetic
• VDJ Recombinases