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Pathologic and biologic study of extranodal lymphomas for the clarification of its molecular pathogenesis

结外淋巴瘤的病理和生物学研究以阐明其分子发病机制

基本信息

批准号：
10670188
负责人：
NAKAMURA Shigeo
金额：
$ 2.37万
依托单位：
Aichi Cancer Center
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

In a recent year, much interest is focused on the biologic behavior of extranodal lymphomas, especially of mucosa-associated lymphoid tissue (MALT) type. The t(11;18)(q21;q21) translocation is a characteristic chromosomal aberration in low-grade B-cell lymphoma of MALT type. We have 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. 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 BAC193f9. The breakpoints at 18q21 in three of the five MALT lymphoma patients were found to be clustered approximately within the 20kb 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 CD22β and laminin 5 α3b subunit. We refereed to the gene encoding this transcript as MALT1. The alteration of MALT1 by translocation strongly suggested that this gene plays an important role in the pathogenesis of MALT lymphoma. Notably, among them, MALT lymphoma with API2-MALT1 gene expression appeared to constitute a homogeneous disease entity. The microscopic appearance is distinctive enough for the diagnosis to be made or at least entertained in routine sections. Their anatomical sites also preferred to lung, intestine, and less commonly stomach. In addition, gastric MALT lymphoma with the genetic alteration of API2-MALT1 seemed to have no relationship with Helicobacter pylori infection. The presence of this set of features in this distinctive tumors has not been sufficiently emphasized in previous reports.

近年来，淋巴结淋巴瘤，特别是粘膜相关淋巴组织（MALT）型淋巴瘤的生物学行为受到广泛关注。t（11;18）（q21;q21）易位是MALT型低度恶性B细胞淋巴瘤的特征性染色体畸变。我们已经确定了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。我们进一步缩小了断点区域在18 q21的5例MALT淋巴瘤患者通过FISH和Southern印迹分析使用的质粒重叠群从BAC 193 f9构建。在5例MALT淋巴瘤患者中，有3例患者的18 q21断裂点被发现聚集在约20 kb区域内。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 α3b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。MALT 1基因的易位改变提示该基因在MALT淋巴瘤的发病中起重要作用。值得注意的是，其中，MALT淋巴瘤与API 2-MALT 1基因表达似乎构成一个同质的疾病实体。显微镜下的表现足以做出诊断，或者至少在常规切片中进行诊断。它们的解剖部位也偏好于肺、肠和胃，较少见。此外，伴有API 2-MALT 1基因改变的胃MALT淋巴瘤似乎与幽门螺杆菌感染无关。这组特征在这种独特的肿瘤中的存在在以前的报告中没有得到足够的强调。