Dataset Information

Favorable role of IDH1/2 mutations aided with MGMT promoter gene methylation in the outcome of patients with malignant glioma.

ABSTRACT:

Aim

The implications of molecular biomarkers IDH1/2 mutations and MGMT gene promoter methylation were evaluated for prognostic outcome of glioma patients.

Materials & methods

Glioma cases were analyzed for IDH1/2 mutations and MGMT promoter methylation by DNA sequencing and methylation-specific PCR, respectively.

Results

Mutations found in IDH1/2 genes totaled 63.4% (N = 40) wherein IDH1 mutations were significantly associated with oligidendrioglioma (p = 0.005) and astrocytoma (p = 0.0002). IDH1 mutants presented more, 60.5% in MGMT promoter-methylated cases (p = 0.03). IDH1 mutant cases had better survival for glioblastoma and oligodendrioglioma (log-rank p = 0.01). Multivariate analysis confirmed better survival in MGMT methylation carriers (hazard ratio [HR]: 0.59; p = 0.031). Combination of both biomarkers showed better prognosis on temozolomide (p < 0.05).

Conclusion

IDH1/2 mutations proved independent prognostic factors in glioma and associated with MGMT methylation for better survival.

SUBMITTER: Pandith AA

PROVIDER: S-EPMC7849969 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Favorable role of <i>IDH</i>1/2 mutations aided with <i>MGMT</i> promoter gene methylation in the outcome of patients with malignant glioma.

Pandith Arshad A AA Qasim Iqbal I Baba Shahid M SM Koul Aabid A Zahoor Wani W Afroze Dil D Lateef Adil A Manzoor Usma U Bhat Ina A IA Sanadhya Dheera D Bhat Abdul R AR Ramzan Altaf U AU Mohammad Fozia F Anwar Iqra I

Future science OA 20201209 3

<h4>Aim</h4>The implications of molecular biomarkers <i>IDH</i>1/2 mutations and <i>MGMT</i> gene promoter methylation were evaluated for prognostic outcome of glioma patients.<h4>Materials & methods</h4>Glioma cases were analyzed for <i>IDH</i>1/2 mutations and <i>MGMT</i> promoter methylation by DNA sequencing and methylation-specific PCR, respectively.<h4>Results</h4>Mutations found in <i>IDH</i>1/2 genes totaled 63.4% (N = 40) wherein <i>IDH</i>1 mutations were significantly associated with ...[more]

PMID: 33552543

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Project description:BackgroundThe prediction of clinical behavior, response to therapy, and outcome of infiltrative glioma is challenging. On the basis of previous studies of tumor biology, we defined five glioma molecular groups with the use of three alterations: mutations in the TERT promoter, mutations in IDH, and codeletion of chromosome arms 1p and 19q (1p/19q codeletion). We tested the hypothesis that within groups based on these features, tumors would have similar clinical variables, acquired somatic alterations, and germline variants.MethodsWe scored tumors as negative or positive for each of these markers in 1087 gliomas and compared acquired alterations and patient characteristics among the five primary molecular groups. Using 11,590 controls, we assessed associations between these groups and known glioma germline variants.ResultsAmong 615 grade II or III gliomas, 29% had all three alterations (i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. Among 472 grade IV gliomas, less than 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had only TERT mutations. The mean age at diagnosis was lowest (37 years) among patients who had gliomas with only IDH mutations and was highest (59 years) among patients who had gliomas with only TERT mutations. The molecular groups were independently associated with overall survival among patients with grade II or III gliomas but not among patients with grade IV gliomas. The molecular groups were associated with specific germline variants.ConclusionsGliomas were classified into five principal groups on the basis of three tumor markers. The groups had different ages at onset, overall survival, and associations with germline variants, which implies that they are characterized by distinct mechanisms of pathogenesis. (Funded by the National Institutes of Health and others.).