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Detection of 11q13 rearrangements in hematologic neoplasias by double-
color fluorescence in situ hybridization
LJ Coignet, E Schuuring, RE Kibbelaar, TK Raap, KK Kleiverda, MF Bertheas, J Wiegant, G Beverstock and PM Kluin
Department of Pathology, University of Leiden, The Netherlands.
Rearrangements within the chromosome 11q13 region are frequent in
hematologic malignancies. 50% of 75% of mantle cell lymphomas (MCLs) carry
a translocation t(11;14) (q13;q32). Using Southern blot analysis, a BCL1
breakpoint can be detected in approximately 50% of MCLs. It is not known
whether other MCLs harbor also breakpoints at 11q13. Breakpoints in this
region not involved in t(11;14), are detected in chronic lymphocytic
leukemia and acute myeloid leukemia. To detect and localize breakpoints at
11q13 more accurately, we have developed fluorescence in situ hybridization
using two probe sets of differently labeled cosmids, symmetrically
localized at either side of the major translocation cluster of BCL1. These
probes span a region of 450 to 750 kb. We applied this assay to a series of
hematologic malignancies with 11q13 abnormalities identified by classical
cytogenetics. All four samples with a t(11;14) (q13;q32) showed
dissociation of the differently colored signals in metaphase and interphase
cells, thereby indicating a chromosomal break in the region defined by the
probe sets. The frequency of abnormal metaphase and interphase cells was
comparable with that observed in any of the 13 malignancies with other
chromosomal 11q13 abnormalities, indicating that these chromosomal breaks
occurred outside the 450- to 750-kb region covered by the probes. One
patient showed triplication and one patient showed monoallelic loss of this
region. The current data show that double-color fluorescence in situ
hybridization is a simple and reliable method for detection of the
t(11;14)(q13;q32) in interphase cell nuclei and that is can be used to
distinguish this translocation from other 11q13 rearrangements in
hematologic malignancies.
Volume 87,
Issue 4,
pp. 1512-1519,
02/15/1996
Copyright © 1996 by The American Society of Hematology
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