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    The t(9; 14)(p13; q32) Chromosomal Translocation Associated With Lymphoplasmacytoid Lymphoma Involves the PAX-5 Gene


    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:

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