MALT1 is deregulated by both chromosomal translocation and amplification in B-cell non-Hodgkin lymphoma
MALT1 is deregulated by both chromosomal translocation and amplification in B-cell non-Hodgkin lymphoma
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DOI：
10.1182/blood-2002-10-3236
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发表时间：
2003-06-01
期刊：
影响因子：
20.3
通讯作者：
Martinez-Climent, JA
中科院分区：
文献类型：
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作者：
Sanchez-Izquierdo, D;Buchonnet, G;Martinez-Climent, JA
MALT 1基因通过其参与t（11;18）（q21;q21）而被鉴定，在30%的粘膜相关淋巴组织（MALT）淋巴瘤病例中可见。在此，我们发现MALT 1表达失调可能发生在各种组织学亚型的B细胞非霍奇金淋巴瘤（B-NHL）中，通过易位到免疫球蛋白重链（IGH）位点或通过基因组扩增。首先，2例MALT淋巴瘤和另一例侵袭性边缘区淋巴瘤（MZL）伴t（14; 18）（q32;荧光原位杂交（FISH）结果显示，与BCL 2易位相同的MALT 1位于BCL 2的5 Mb左右的着丝粒。通过长距离反向聚合酶链反应的分子克隆显示，断点位于第一个5'MALT 1外显子的1至2 kb的着丝粒处;两例病例均显示MALT 1在RNA或蛋白质水平过表达。其次，我们研究了结构和基因表达谱的基因组扩增涉及18 q21在一组40 B-NHL细胞系使用比较基因组杂交芯片（阵列CGH）和基因表达谱技术。使用阵列CGH，观察到2个基因组扩增峰，一个以BCL 2为中心，另一个以MALT 1为中心。在具有MALT 1扩增的3个细胞系中，通过基因分析、定量逆转录-聚合酶链反应（QRT-PCR）和蛋白质印迹法评估，2个显示MALT 1过表达。为了确定原发性MALT和脾MZL肿瘤中是否发生了类似的事件，通过FISH或QRT-PCR分析了40例病例;在2例病例中观察到基因组扩增和MALT 1过表达。总之，这些数据暗示MALT 1作为一种显性癌基因，可能在B-NHL的发病机制中发挥作用。(C)2003年，美国血液学会。
The MALT1 gene was identified through its involvement in t(11;18)(q21;q21), seen in 30% of cases of mucosa-associated, lymphoid tissue (MALT) lymphoma. Here, we show that deregulated MALT1 expression may occur in B-cell non-Hodgkin lymphoma (B-NHL) of various histologic subtypes either through translocation to the immunoglobulin heavy chain (IGH) locus or by genomic amplification, First, 2 cases, one case of MALT lymphoma and another of aggressive marginal zone lymphoma (MZL) with t(14;1 8)(q32;q21), cytogenetically identical to the translocation involving BCL2 Were shown by fluorescence in situ hybridization (FISH) to involve MALT1, which lies about 5 Mb centromeric of BCL2. Molecular cloning of both by long-distance inverse polymerase chain reaction showed breakpoints lying 1 to 2 kilobase (kb) centromeric of the first 5' MALT1 exon; both cases showed MALT1 overexpression at either RNA or protein levels. Second, we examined the structure and gene expression profile of genomic amplifications involving 18q21 in a panel of 40 B-NHL cell lines using comparative genomic hybridization to microarrays (array CGH) and gene expression profiling techniques. Using array CGH, 2 peaks of genomic amplification were observed one centered around BCL2 and the other around MALT1. Of the 3 cell lines with MALT1 Amplification, 2 showed MALT1 overexpression as assessed by gene profiling, quantitative reverse transcription-polymerase chain re action (QRT-PCR), and Western blotting. To determine if comparable events occurred in primary MALT and splenic MZL tumors, 40 cases were analyzed by FISH or QRT-PCR; genomic amplification and MALT1 overexpression were seen in 2 cases. Together, these data implicate MALT1 as a dominant oncogene that may play a role in the pathogenesis of B-NHL. (C) 2003 by The American Society of Hematology.