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Direct sequence analysis of the 14q+ and 18q- chromosome junctions in
follicular lymphoma
F Cotter, C Price, E Zucca and BD Young
Imperial Cancer Research Fund, Medical Oncology Unit, St Bartholomew's
Hospital, London, UK.
Although the t(14;18) chromosome translocation has been demonstrated to be
a highly consistent feature of follicular lymphomas, the underlying
mechanism generating this fusion has remained uncertain. To examine this
question further, a polymerase chain reaction strategy has been devised to
permit the amplification and direct sequencing of the resultant 14q+ and
18q- reciprocal junctions. Direct sequence analysis of amplified 14q+
junctions established that 7 of 11 tumors contained a bcl-2 (mbr) sequence
fused to an immunoglobulin JH region (five were J6 and two were J5). One of
these junctions had an unusual configuration with the bcl-2 and JH
sequences separated by a recognizable DH region. This finding suggests that
at least some of the junctional sequences, previously thought of as N
insertions, may be fragments of unrecognized DH regions. It was also
possible to amplify and sequence 18q- junctions using a primer based on the
DH recombination signal sequences. Several 18q- junctions were shown to
consist of DH/bcl-2 (either mbr or mcr) fusions. In two tumors the 14q+ and
18q- junctions were fully sequenced, and it was demonstrated that the bcl-2
sequence was conserved during mbr and mcr translocations. This contrasts
with previous analyses that demonstrated either loss or duplication of
several bases at the breakpoints in the bcl-2 gene.
Volume 76,
Issue 1,
pp. 131-135,
07/01/1990
Copyright © 1990 by The American Society of Hematology
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