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Blood, Vol. 92 No. 8 (October 15), 1998:
pp. 2871-2878
DNA Fiber Fluorescence In Situ Hybridization Analysis of
Immunoglobulin Class Switching in B-Cell Neoplasia: Aberrant
CH Gene Rearrangements in Follicle Center-Cell Lymphoma
Jan-Willem Vaandrager,
Ed Schuuring,
Hanneke C. Kluin-Nelemans,
Martin J.S. Dyer,
Anton K. Raap, and
Philip M. Kluin
From the Department of Pathology, the Department of Hematology, and
the Department of Cytometry and Cytochemistry, Leiden University
Medical Centre, Leiden, The Netherlands; and the Academic Department of
Hematology and Cytogenetics, ICR, Royal Marsden Hospital, Sutton, UK.
Immunoglobulin class switching usually involves deletion of part of
the immunoglobulin CH region. By DNA fiber fluorescence in
situ hybridization (FISH) with a barcode of probes covering the
DH, JH, and CH genes, the
configuration of the entire CH region can be visualized on
single DNA molecules. Using this technique, we have studied class
switching in three types of B-cell neoplasia, mantle-cell lymphoma
(MCL), follicular lymphoma (FL) and hairy cell leukemia (HCL),
representing B cells in, respectively, pregerminal center, germinal
center, and postgerminal center stages of development. In MCL and FL,
simultaneous detection of the t(11;14) and t(14;18) breakpoint with
probes for the BCL-1 and BCL-2 loci, respectively, allowed
differentiation between productive and nonproductive alleles. In none
of 10 MCL cases was class switching detected. In 21 HCL, all
nonimmunoglobulin M (IgM) cases had class-switch deletion consistent
with the expressed isotype on at least one allele. In FL, however, a
peculiar pattern of CH rearrangement was observed. In IgM
expressing FL, the translocated alleles had switched in 11 of 13 cases,
and the nontranslocated allele showed complex rearrangements downstream
from the Cµ-C genes in 9 of 13 cases. These downstream
rearrangements may reflect tumor-specific deregulation of the
class-switch machinery. All seven immunoglobulin G (IgG) expressing FL
showed class switching on both alleles. Fiber FISH analysis also showed
several polymorphisms. The most frequent one, present on 38% of all
analyzed alleles, consisted of an extra C gene or pseudogene in the
3 cluster.
© 1998 by The American Society of Hematology.
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