Variable breakpoints in Burkitt lymphoma cells with chromosomal t(8;14) translocation separate c-myc and the IgH locus up to several hundred kb.
In about 80% of Burkitt's lymphoma cases, the tumour cell harbours a reciprocal chromosomal translocation which invariably transposes the coding exons 2 and 3 of c-myc from chromosome 8 to the immunoglobulin heavy chain locus on chromosome 14. Those t(8;14) translocations which disrupt chromosome 8 within or close to the c-myc gene are well documented. In this study we have focussed on t(8;14) translocations with the chromosomal breakpoint far upstream of c-myc. We analyzed the breakpoint position in 44 BL cell lines with t(8;14) translocations of different geographical origin and identified 9 cell lines with the breakpoint more than 14 kb upstream of c-myc. In these cell lines the positions of the translocation junctions on the derivative chromosomes 8q- and 14q+ were mapped by pulsed field gel electrophoresis and multicolour fluorescence in situ hybridization. The breakpoints occur at distances between 55 and more than 340 kb upstream of c-myc with no preferential site on chromosome 8. On chromosome 14, however, the translocation breakpoints are clustered in a narrow region 5' of the intron enhancer of the immunoglobulin heavy chain gene. In 7 of 9 cases, the enhancer is fused to the c-myc bearing sequences of chromosome 8. In two cases, the translocation has occurred in switch mu and downstream of C mu, respectively. The impact of these results with respect to the hypothesis, that cis-regulatory sequences from the immunoglobulin heavy chain locus can deregulate c-myc expression in a manner sufficient for tumour formation, is discussed.
Joos
S
S
GSF-Forschungszentrum für Umwelt und Gesundheit GmbH, Institut für Klinische Molekularbiologie und Tumorgenetik, München, Germany.
Falk
M H
MH
Lichter
P
P
Haluska
F G
FG
Henglein
B
B
Lenoir
G M
GM
Bornkamm
G W
GW
D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14; D002898:Chromosomes, Human, Pair 8; D004277:DNA, Single-Stranded; D004742:Enhancer Elements, Genetic; D016259:Genes, myc; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D008969:Molecular Sequence Data; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D004277:DNA, Single-Stranded; D007143:Immunoglobulin Heavy Chains