Detection of messenger RNA from O6-methylguanine-DNA methyltransferase gene MGMT in human normal and tumor tissues.
BACKGROUND
The level of the DNA repair protein O6-methylguanine-DNA methyltransferase is an important determinant of the response of tumor cells in culture to alkylating nitrosoureas. In these cells, the abundance of messenger RNA (mRNA) is directly correlated with repair activity.


OBJECTIVE
Our purpose was to compare transferase mRNA levels with the repair activity in primary human tumors.


METHODS
Human transferase mRNA was measured in tissue samples from brain tumors, normal lung, lung tumors, ovarian tumors, and normal human liver by use of an RNA protection assay with an antisense probe prepared from the cloned gene.


RESULTS
Normal and tumor tissue samples from the same patient had similar transferase activity levels, but transferase expression varied widely among tissue samples from different patients. Brain and lung samples, on average, had transferase mRNA levels closer to those in liver samples than their transferase activity levels. In two cases, tissue samples which were transferase deficient by the activity assays were found to lack transferase mRNA.


CONCLUSIONS
Deficiencies in transferase activity are due to reduced or absent mRNA transcription or processing. In brain and lung, there may be post-transcriptional control of mRNA expression. The wide interindividual variation in transferase expression is also seen at the transcription level.


CONCLUSIONS
These are among the first measures of transferase mRNA expression in primary human tissue. More samples should be examined to extend these observations.
Citron
M
M
Division of Hematology/Oncology, Long Island Jewish Medical Center, New Hyde Park, NY 11042.
Graver
M
M
Schoenhaus
M
M
Chen
S
S
Decker
R
R
Kleynerman
L
L
Kahn
L B
LB
White
A
A
Fornace
A J
AJ
Yarosh
D
D
D001932:Brain Neoplasms / Q000201:enzymology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008175:Lung Neoplasms / Q000201:enzymology; D008780:Methyltransferases / Q000235:genetics*; D009369:Neoplasms / Q000201:enzymology*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D009928:Organ Specificity; D010051:Ovarian Neoplasms / Q000201:enzymology; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase