Microsatellite instability and expression of DNA mismatch repair genes in malignant astrocytic tumors from adult and pediatric patients.
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.
Szybka
M
M
Department of Pathology, Chair of Oncology, Medical University of Lodz , Poland.
Bartkowiak
J
J
Zakrzewski
K
K
Polis
L
L
Liberski
P
P
Kordek
R
R
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001254:Astrocytoma / Q000235:genetics*; D020137:Base Pair Mismatch / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D002352:Carrier Proteins; D016543:Central Nervous System Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D005819:Genetic Markers; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein