Szybka M, Bartkowiak J, Zakrzewski K, Polis L, Liberski P, Kordek R
Department of Pathology, Chair of Oncology, Medical University of Lodz , Poland.
Clin Neuropathol. 2003 Jul-Aug;22(4):180-6.
Microsatellite instability (MSI) is used as a molecular marker for defective DNA mismatch repair (MMR) genes. We report here alterations of MSI in 15 malignant astrocytomas (WHO grade III) and glioblastomas (GBM; WHO grade IV) of pediatric patients (2 - 21 years) and 12 GBM from adults (44 - 68 years) by comparative analysis of BAT25/BAT26 loci and 10 other microsatellite markers. High-level microsatellite instability (MSI-H) occurred in 4 of the 15 pediatric cases (26.7%) and in 1 of the 12 adult GBM cases (8.3%). Low-level microsatellite instability (MSI-L) was observed in 6 pediatric cases (40%) and 8 adult GBM (66.7%). Unstable BAT-25 locus was found in 1 of the MSI-H pediatric cases. Thus, 2 unstable cases showed no instability of this marker. For BAT-26, such a discordance was even more profound: in 1 of MSI-H cases, we obtained no PCR product and the remaining 3 showed no alterations of this marker. MSH2 (Human MutS, Homologue2) protein was detected in all but 3 pediatric cases (1 highly unstable and 2 low-level unstable) and in all adult cases. MLH1 (Human MutL, Homologue 1) protein was detected in all but 2 pediatric cases (1 highly unstable and 1 low-level unstable). Thus, 2 highly unstable pediatric cases showed no detectable MLH1/MSH2 proteins. Our data support earlier observations that MSI occurs predominantly in malignant astrocytic tumors of young patients, which lends support to the hypothesis of different molecular mechanisms of pediatric brain tumors. Surprisingly, we found no significant correlation between the status of 10 microsatellite markers and that of either BAT25 or BAT26 loci or with the expression of MMR genes.
微卫星不稳定性（MSI）被用作DNA错配修复（MMR）基因缺陷的分子标志物。我们通过对BAT25/BAT26位点及其他10个微卫星标志物进行比较分析，报告了15例儿科患者（2至21岁）的恶性星形细胞瘤（世界卫生组织III级）和胶质母细胞瘤（GBM；世界卫生组织IV级）以及12例成人GBM（44至68岁）中MSI的改变情况。15例儿科病例中有4例（26.7%）出现高水平微卫星不稳定性（MSI-H），12例成人GBM病例中有1例（8.3%）出现MSI-H。6例儿科病例（40%）和8例成人GBM（66.7%）观察到低水平微卫星不稳定性（MSI-L）。在1例MSI-H儿科病例中发现BAT-25位点不稳定。因此，有2例不稳定病例该标志物未表现出不稳定性。对于BAT-26，这种不一致更为明显：在1例MSI-H病例中未获得PCR产物，其余3例该标志物未显示改变。除3例儿科病例（1例高度不稳定和2例低水平不稳定）外，所有儿科病例均检测到MSH2（人类MutS同源物2）蛋白，所有成人病例也均检测到该蛋白。除2例儿科病例（1例高度不稳定和1例低水平不稳定）外，所有儿科病例均检测到MLH1（人类MutL同源物1）蛋白。因此，2例高度不稳定的儿科病例未检测到可检测的MLH1/MSH2蛋白。我们的数据支持了早期的观察结果，即MSI主要发生在年轻患者的恶性星形细胞肿瘤中，这为儿童脑肿瘤不同分子机制的假说提供了支持。令人惊讶的是，我们发现10个微卫星标志物的状态与BAT25或BAT26位点的状态或与MMR基因的表达之间均无显著相关性。
