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INACTIVE REPAIR GENE PREDICTS OUTCOMES FOR BRAIN TUMOR PATIENTS

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  2. INACTIVE REPAIR GENE PREDICTS OUTCOMES FOR BRAIN TUMOR PATIENTS

Gliomas that show inactivity in the DNA repair enzyme MGMT may be more responsive to chemotherapy, according to a study in the New England Journal of Medicine (2000;343: 1350-1354). 

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Figure  . Gllomas and chemotherapy

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Scientists at Johns Hopkins Oncology Center analyzed grade III or IV gliomas from 47 patients, all of whom were treated with carmustine (BCNU), the standard chemotherapy agent used for gliomas. The study found that in 19 of the 47 samples (40%), the MGMT gene was methylated—meaning that a methyl group attached to the promoter region of the gene, shutting down MGMT function.

When the MGMT protein is active in tumor tissue, it rapidly repairs chemotherapy-induced DNA muta-tions in tumor cells, rendering drugs that work by this mechanism useless. Fortunately, about 30% of gliomas have a methylated MGMT gene.

A methylated MGMT gene was associated with better overall and disease-free survival, the study found. Sixty-three percent of the patients with inactivated MGMT had a partial or complete response to drug therapy, compared with only 4% of those whose MGMT capability was intact. The status of the MGMT gene was a better predictor of the patient's response to treatment than even the grade of the tumor or the patient's age.

The status of the MGMT gene was a better predictor of the patient's response to treatment than even the grade of the tumor or the patient's age.

Further studies are needed to confirm the value of MGMT DNA repair activity to predict how patients will respond to treatment. If results are consistent, chemotherapy might be reserved for those most likely to respond.

In the future, it may also be possible to increase the sensitivity of resistant tumors to chemotherapy by using drugs that inhibit the MGMT enzyme.