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The t(9;14)(p13;q32) chromosomal translocation associated with
lymphoplasmacytoid lymphoma involves the PAX-5 gene
S Iida, PH Rao, P Nallasivam, H Hibshoosh, M Butler, DC Louie, V Dyomin, H Ohno, RS Chaganti and R Dalla-Favera
Department of Pathology, College of Physicians and Surgeons, Columbia
University, New York, NY 10032, USA.
The t(9;14)(p13;q32) translocation is associated with approximately 50% of
lymphoplasmacytoid lymphoma (LPL), a subtype of B-cell non-Hodgkin's
lymphoma (NHL). We cloned the chromosomal breakpoint of der (14) from an
LPL case (1052) and showed that it involved a junction between 9p13 and the
switch micro region of the Ig heavy chain locus (IgH) on 14q32. Using a YAC
contig spanning 1.5 megabase (Mb), we determined that the 9p13 breakpoint
in one case (1052) mapped within a 270-kb restriction fragment containing
two previously reported 9p breakpoints associated with a alpha-heavy chain
disease case (MAL) and KI-1 positive diffuse large cell lymphoma (DLCL)
cell line (KIS-1). The same fragment also contained the PAX-5 gene which
encodes a B-cell specific transcription factor involved in the control of
B-cell proliferation and differentiation. The breakpoints of KIS-1 and 1052
were mapped within the 5' noncoding region of PAX-5, while the 9p13
breakpoint of MAL mapped 230 to 270 kb upstream to PAX-5. In all three
cases, the translocation caused the juxtaposition of the PAX-5 gene to the
IgH locus in the opposite direction of transcription. When compared with
six other DLCL cell lines lacking t(9;14)(p13;q32), the KIS-1 cell line
showed an 11-fold overexpression of PAX-5 mRNA and a significantly reduced
expression of the p53 gene, which is normally regulated by PAX- 5.
Moreover, metaphase and interphase fluorescence in situ hybridization
(FISH) analysis using a YAC clone spanning 1 Mb including the PAX-5 as a
probe identified chromosomal translocations in 5 of 7 cases carrying 9p13
translocations. These findings suggest that the PAX- 5 gene is the target
of the t(9;14) in LPL whereby its expression may be deregulated by
juxtaposition to IgH regulatory elements, thus contributing to
lymphomagenesis.
Volume 88,
Issue 11,
pp. 4110-4117,
12/01/1996
Copyright © 1996 by The American Society of Hematology
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