K. Stamatopoulos et al., Molecular analysis of bcl-1/IgH junctional sequences in mantle cell lymphoma: potential mechanism of the t(11;14) chromosomal translocation, BR J HAEM, 105(1), 1999, pp. 190-197
Mantle cell lymphoma (MCL) is characterized by the t(11;14) translocation t
hat juxtaposes the bcl-1 locus to immunoglobulin (Ig) gene sequences and le
ads to deregulation of cyclin D1 gene, t(11;14) is thought to result from a
n error of the recombinase during D-TH Ig gene assembly; however, data on t
he underlying mechanism and candidate recombination-targeting motifs in the
major translocation cluster (MTC) of the bcl-1 gene are lacking.
bcl-1/IgH junctional sequences from seven MCL patients were amplified by PC
R using primers targeting MTC and J(H) sequences on chromosomes 11q13 and 1
4q32, respectively. PCR products were directly sequenced and junctional seq
uences were searched for homology to known germline D genes. bcl-t MTC brea
kpoints were searched for the presence of possible recombination target mot
ifs; heptamers, nonamers, binding sequence of the bp45 nuclease, x-like seq
uences and D gene segments.
bcl-1/J(H) junctions were found to bear homology to D gene segments (DLR3,
DM and DIR5) in 3/7 MCL samples. A computer-based search in previously publ
ished and/or submitted to GenBank bcl-1/J(H) junctional sequences identifie
d homology to D genes in 1/4 MCL tumour samples and 1/4 MCl cell lines; DXP
4 or D23/7 and DHQ52 or D22/21 or DXP5, respectively. The MTC locus contain
ed motifs with homology to bp45 nuclease binding sequence, x-like sequences
, heptamers/nonamers, D-like DIR genes and nonhomologous recombination shor
t (6 bp) DNA sequences.
The above data indicate that the t(11;14) translocation in MCL may also occ
ur at a more mature stage of B-cell ontogeny than previously thought, i.e.
during V-H-to-DJ(H) rearrangement. Various known recombination motifs withi
n MTC may contribute to an illegitimate recombination event between bcl-1 a
nd DJ(H).