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Detection of the chromosomal translocation t(11;14) by polymerase chain
reaction in mantle cell lymphomas
R Rimokh, F Berger, G Delsol, I Digonnet, JP Rouault, JD Tigaud, M Gadoux, B Coiffier, PA Bryon and JP Magaud
Laboratoire d'Hematologie et de Cytogenetique, Hopital Edouard Herriot,
Lyon, France.
The t(11;14)(q13;q32) and its molecular counterpart, BCL1 rearrangement,
are consistent features of mantle cell lymphoma (MCL). Rearrangement is
thought to deregulate the nearby CCND1 (BCL1/PRAD1) proto-oncogene, a
member of the cyclin G1 gene family, and thereby to contribute to
tumorigenesis. We and others have previously shown that the BCL1 locus is
rearranged in 55% to 60% of MCL patients and that, on chromosome 11, more
than 80% of the breakpoints are localized within a 1-kbp DNA segment known
as the major translocation cluster (MTC). We have determined the nucleotide
sequence for a portion of the MTC region, and constructed chromosome
11-specific oligonucleotides that were in conjunction with a consensus
immunoglobulin (Ig) heavy chain joining region (JH) primer used to perform
the polymerase chain reaction (PCR) to amplify t(11;14) chromosomal
junctional sequences in DNA from 16 MCL patients with breakpoints in the
MTC region. 15 of the 16 breakpoints that occurred at the MTC region were
amenable to PCR detection. The sizes of the amplified bands, the existence
or not of a Sac I site in the PCR products, and nucleotide sequencing of
the amplified DNA from four patients showed that the breakpoints share a
remarkable tendency to tightly cluster within 300 bp on chromosome 11, some
of them occurring at the same nucleotide. On chromosome 14, the breakpoints
were localized within the Ig JH. Our findings indicate that a BCL1
rearrangement can be detected using this approach in roughly one half of
the MCL patients. This has implications for both the diagnosis and the
clinical management of MCL.
Volume 83,
Issue 7,
pp. 1871-1875,
04/01/1994
Copyright © 1994 by The American Society of Hematology
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