The t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmacytoid lymphoma involves the PAX-5 gene.
The t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmacytoid lymphoma involves the PAX-5 gene.
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DOI：
10.1182/blood.v88.11.4110.bloodjournal88114110
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发表时间：
1996
期刊：
影响因子：
20.3
通讯作者：
Shinsuke Lida;P. Rao;P. Nallasivam;H. Hibshoosh;Marion P. Butler;D. Louie;V. Dyomin;H. Ohno;R. Chaganti;R. Dalla-Favera
中科院分区：
文献类型：
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作者：
Shinsuke Lida;P. Rao;P. Nallasivam;H. Hibshoosh;Marion P. Butler;D. Louie;V. Dyomin;H. Ohno;R. Chaganti;R. Dalla-Favera
t(9;14)(p13;q32) 易位与大约 50% 的淋巴浆细胞样淋巴瘤 (LPL) 相关，LPL 是 B 细胞非霍奇金淋巴瘤 (NHL) 的一种亚型。我们从 LPL 病例 (1052) 中克隆了 der (14) 的染色体断点，并表明它涉及 9p13 和 14q32 上 Ig 重链基因座 (IgH) 的开关微区之间的连接。使用跨越 1.5 兆碱基 (Mb) 的 YAC 重叠群，我们确定一个病例 (1052) 中的 9p13 断点映射在 270 kb 限制性片段内，其中包含两个先前报道的与 α 重链疾病病例 (MAL) 和 KI-1 阳性弥漫性大细胞淋巴瘤 (DLCL) 细胞系 (KIS-1) 相关的 9p 断点。同一片段还包含 PAX-5 基因，该基因编码参与控制 B 细胞增殖和分化的 B 细胞特异性转录因子。 KIS-1 和 1052 的断点映射在 PAX-5 的 5' 非编码区域内，而 MAL 的 9p13 断点映射到 PAX-5 上游 230 至 270 kb。在所有三种情况下，易位导致 PAX-5 基因与 IgH 基因座以相反的转录方向并置。与其他六种缺乏 t(9;14)(p13;q32) 的 DLCL 细胞系相比，KIS-1 细胞系显示 PAX-5 mRNA 过表达 11 倍，而 p53 基因的表达显着降低，而 p53 基因通常受 PAX-5 调节。此外，使用跨越 1 Mb 的 YAC 克隆（包括 PAX-5 作为探针）进行中期和间期荧光原位杂交 (FISH) 分析，在 7 个携带 9p13 易位的病例中，鉴定出 5 个染色体易位。这些发现表明，PAX-5 基因是 LPL 中 t(9;14) 的靶标，因此其表达可能通过与 IgH 调节元件并置而失调，从而促进淋巴瘤发生。
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.