A novel gene, MALT1 at 18q21, is involved in t(11;18) (q21;q21) found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue

A novel gene, MALT1 at 18q21, is involved in t(11;18) (q21;q21) found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue
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DOI:
10.1038/sj.onc.1203018
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发表时间:
1999-10-14
期刊:
影响因子:
8
通讯作者:
Seto, M
Seto, M
中科院分区:
医学1区
文献类型:
--
作者:
Akagi, T;Motegi, M;Seto, M

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t(11; 18)(q21; q21)易位是粘膜相关淋巴组织(MALT)型低度恶性B细胞淋巴瘤的特征性染色体畸变。我们以前确定了YAC克隆y 789 F3,其中包括在MALT淋巴瘤患者的18 q21的断点。在YAC上构建BAC和PAC重叠群,发现BAC 193 f9包含断点区域。本研究利用BAC 193 f9构建的质粒重叠群,通过FISH和Southern印迹分析,进一步缩小了5例MALT淋巴瘤患者18 q21断裂点的范围。通过使用外显子扩增和cDNA文库筛选,我们确定了一种新的cDNA跨越断点区域,表现出异常的mRNA信号在四个MALT淋巴瘤患者。核苷酸序列预测了一个813个氨基酸的蛋白质,其显示出与CD 22 β和层粘连蛋白5 α 3b亚基的显著序列相似性。我们将编码该转录本的基因称为MALT 1(粘膜相关类淋巴瘤组织淋巴瘤易位基因1)。MALT 1基因的易位改变提示该基因在MALT淋巴瘤的发病机制中起重要作用。
The t(11;18) (q21;q21) translocation is a characteristic chromosomal aberration in low-grade B-cell lymphoma of mucose-associated lymphoid tissue (MALT) type. We previously identified a YAC clone y789F3, which includes the breakpoint at 18q21 in a MALT lymphoma patient. BAC and PAC contigs were constructed on the YAC, and BAC 193f9 was found to encompass the breakpoint region. In the present study, we further narrowed down the breakpoint region at 18q21 in five MALT lymphoma patients by means of FISH and Southern blot analyses using the plasmid contig constructed from BAC 193f9, The breakpoints at 18q21 in three of the five MALT lymphoma patients were found to be clustered approximately within the 20 kb region. By using exon amplification and cDNA library screening, we identified a novel cDNA spanning the breakpoint region that exhibited aberrant mRNA signals in four of the five MALT lymphoma patients. The nucleotide sequence predicted an 813 amino acid protein that shows significant sequence similarity to the CD22 beta and laminin 5 alpha 3b subunit, We refer to the gene encoding this transcript as MALT1 (Mucosa-Associated Lymphoid Tissue lymphoma translocation gene 1). The alteration of MALT1 by translocation strongly suggests that this gene plays an important role in the pathogenesis of MALT lymphoma.