Lida, Shinsuke and Rao, Pulivarthi H. and Nallasivam, Palanisamy and Hibshoosh, Hanina and Butler, Marion P. and Louie, Diane C. and Dyomin, Vadim and Ohno, Hitoshi and Chaganti, R.S.K. and Dalla-Favera, Riccardo (1996) The t(9; 14)(p13; q32) Chromosomal Translocation Associated With Lymphoplasmacytoid Lymphoma Involves the PAX-5 Gene. Blood, 88 (11). pp. 4110-4117. ISSN 0006-4971

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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 y region of the Ig heavy chain locus (IgH) on 14q32. Using a VAC 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 a-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 PAX5 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 VAC 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.

Item Type:	Article
Keywords:	t(9;14)(p13;q32); chromosomal translocation; lymphoplasmacytoid lymphoma; PAX-5 gene;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	12364
Identification Number:	https://doi.org/10.1182/blood.V88.11.4110.bloodjournal88114110
Depositing User:	Marion Butler
Date Deposited:	04 Feb 2020 16:54
Journal or Publication Title:	Blood
Publisher:	American Society of Hematology
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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