Niv Eva, Bomstein Yonit, Bernheim Joelle, Lishner Michael
Department of Medicine, Meir Hospital, Kfar-Saba, Israel.
Mod Pathol. 2004 Nov;17(11):1407-13. doi: 10.1038/modpathol.3800207.
The role of microsatellite instability and defects in DNA mismatch repair mechanism in the pathogenesis of gastric lymphoma of mucosa-associated lymphoid tissue (MALT) type is still controversial, as both negative and positive findings have been reported. This may be explained mainly by arbitrary selection of the tested loci, the use of various techniques of microsatellite instability analysis and by different definitions of replication error positive phenotype. The aim of our study was to evaluate the instability at selected microsatellite markers using the GeneScan Analysis Software. DNA from paraffin-embedded tissue blocks of 13 previously untreated patients with localized gastric MALT lymphoma was extracted. Five microsatellite markers, which are located in hMSH2, hMLH1, P16, APC and MLL loci, were selected from the genetic database. We found genetic instability in tumors of 9/13 patients with gastric MALT lymphoma (69%). Seven of them had replication-error-positive phenotype (54%). Microsatellite instability was found in 39% of the samples in the MLL locus, 39% in the APC, 46% in the P16, 23% in the hMLH1 and none in the hMSH2. This study demonstrates that microsatellite instability has more prominent role in pathogenesis of gastric MALT lymphoma than reported to date. We suggest that microsatellite instability should be analyzed with markers adjacent to chromosomal loci that are involved in lymphomas. Our findings support the 'Real Common Target genes' theory of high rate of microsatellite instability in specific genes, which are associated with related tumors.
微卫星不稳定性及DNA错配修复机制缺陷在黏膜相关淋巴组织(MALT)型胃淋巴瘤发病机制中的作用仍存在争议,因为既有阴性结果也有阳性结果的报道。这主要可能是由于检测位点的随意选择、微卫星不稳定性分析技术的多样使用以及复制错误阳性表型的不同定义所致。我们研究的目的是使用基因扫描分析软件评估所选微卫星标记的不稳定性。提取了13例先前未经治疗的局限性胃MALT淋巴瘤患者石蜡包埋组织块中的DNA。从基因数据库中选择了位于hMSH2、hMLH1、P16、APC和MLL位点的5个微卫星标记。我们发现13例胃MALT淋巴瘤患者中有9例(69%)的肿瘤存在基因不稳定性。其中7例具有复制错误阳性表型(54%)。在MLL位点的样本中,39%发现微卫星不稳定性,APC位点为39%,P16位点为46%,hMLH1位点为23%,hMSH2位点未发现。本研究表明,微卫星不稳定性在胃MALT淋巴瘤发病机制中的作用比迄今报道的更为突出。我们建议应使用与淋巴瘤相关的染色体位点相邻的标记来分析微卫星不稳定性。我们的研究结果支持特定基因中微卫星不稳定性高发生率的“真正共同靶基因”理论,这些基因与相关肿瘤有关。