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Interphase and metaphase detection of the breakpoint of 14q32
translocations in B-cell malignancies by double-color fluorescence in situ
hybridization
M Taniwaki, K Nishida, Y Ueda, S Misawa, M Nagai, S Tagawa, T Yamagami, H Sugiyama, M Abe and S Fukuhara
Third Department of Internal Medicine, Kyoto Prefectural University of
Medicine, Japan.
The breakpoint of 14q32 translocations found in B-cell malignancies was
delineated specifically in both metaphase spreads and interphase nuclei by
double-color fluorescence in situ hybridization (FISH) using bacteriophage
clones containing the human immunoglobulin gamma chain gene locus (Ig
gamma) and a cosmid clone, CY24-68, containing VH segments. CY24-68 is more
telomeric than Ig gamma, separated by approximately 1 megabase (Mb). FISH
studies were performed on four patients with non-Hodgkin's lymphoma (NHL),
one with acute lymphoblastic leukemia (ALL), one with plasma cell leukemia
(PCL), and three cell lines. In each patient with t(8;14), t(14;18), and
t(3;14), the signal of Ig gamma gene was observed on der(14) and that of
CY24-68 at respective partner sites of these translocations, 8q24.1,
18q21.3, and 3q27. Interphase nuclei with a signal of Ig gamma clearly
separated from that of CY24-68 were more frequently encountered in all of
the patients (45% to 74%) than those in normal controls (4% to 5%). Even in
cases where only interphase nuclei were available for FISH studies, 14q32
translocations are detected as shown in two patients each with NHL and
t(11;14)-carrying PCL. In two cell lines, HS-1 derived from ALL carrying
t(8;14) and FR4 derived from a plasmacytoma carrying a complex form of
t(8;14), the signal of Ig gamma was observed at the breakpoint region
8q24.1 of the der(8) in addition to the der(14), indicating that
translocation event occurred within the Ig gamma locus. Intense Ig gamma
signal was found at the breakpoint region on the der(14)t(11;14) in HBL-2
derived from NHL, indicating amplification of the Ig gamma gene, and
presumably the resultant chimeric DNA between Ig gamma and DNA sequences at
11q13. The present approach allowed us to unequivocally detect
tumor-specific breakpoints of 14q32 translocations. Furthermore, interphase
FISH provides a rapid diagnostic procedure to detect 14q32 translocations
in B-cell malignancies.
Volume 85,
Issue 11,
pp. 3223-3228,
06/01/1995
Copyright © 1995 by The American Society of Hematology
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