The t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmocytoid lymphoma involves the PAX-5 gene Journal Article

  

Authors:	Iida, S.; Rao, P. H.; Nallasivam, P.; Hibshoosh, H.; Butler, M.; Louie, D. C.; Dyomin, V.; Ohno, H.; Chaganti, R. S. K.; DallaFavera, R.
Article Title:	The t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmocytoid lymphoma involves the PAX-5 gene
Abstract:	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 mu 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. (C) 1996 by The American Society of Hematology.
Keywords:	molecular analysis; differentiation; expression; non-hodgkins-lymphoma; alveolar rhabdomyosarcoma; region; burkitt-lymphoma; large-cell lymphoma; breakpoint; transcription factor bsap
Journal Title:	Blood
Volume:	88
Issue:	11
ISSN:	0006-4971
Publisher:	American Society of Hematology
Date Published:	1996-12-01
Start Page:	4110
End Page:	4117
Language:	English
ACCESSION:	WOS:A1996VV15200004
PROVIDER:	wos
PUBMED:	8943844
DOI:	10.1182/blood.V88.11.4110.4110
Notes:	Article -- Source: Wos

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