Comparison of O6-methylguanine-DNA methyltransferase activity in brain tumors and adjacent normal brain.
We assayed the activity of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) in 60 human brain tumors to assess the effects of tumorigenesis in brain on DNA repair capability. Activity was not detectable (< 0.5 fmol/10(6) cells, i.e., < 300 molecules/cells) in 27% of the tumors. Measurable MGMT varied by more than 2 orders of magnitude, 0.5-104.1 fmol/10(6) cells. Mean tumor MGMT levels did not differ between the sexes but did vary widely between diagnostic groups. A significant inverse correlation was observed between tumor MGMT activity and patient age. We also assayed MGMT activity in overlying, histologically tumor-free brain resected with 25 tumors. Of these samples, 52% had no detectable MGMT activity, and the remainder had activity comparable to that in tumors ranging from 0.7-21.8 fmol/10(6) cells. MGMT activity in normal brain was also inversely correlated with patient age. For 15 of 25 (60%) paired samples, tumor activity was 2 to > 38-fold greater than that of normal brain; for 4 pairs (16%) tumor activity was 2.5 to > 17-fold lower than that of normal brain; the remaining 6 (24%) had no detectable activity in both tumor and normal tissue. These differences in the magnitudes and distributions of activities for tumor versus normal brain tissue were significant (P = 0.02), demonstrating that tumorigenesis in brain is often accompanied by marked elevation of MGMT.
Silber
J R
JR
Department of Neurological Surgery, University of Washington, Seattle 98195.
Mueller
B A
BA
Ewers
T G
TG
Berger
M S
MS
D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000201:enzymology; D001921:Brain / Q000201:enzymology*; D001932:Brain Neoplasms / Q000201:enzymology*; D002648:Child; D002675:Child, Preschool; D004806:Ependymoma / Q000201:enzymology; D005260:Female; D005910:Glioma / Q000201:enzymology; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000201:enzymology; D008780:Methyltransferases / Q000032:analysis*; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase; D009837:Oligodendroglioma / Q000201:enzymology
D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase