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Int. J. Mol. Sci. 2016, 17(11), 1876; doi:10.3390/ijms17111876

Potential Role of Methylation Marker in Glioma Supporting Clinical Decisions

1
Department of Oncology, Radiotherapy and Ginecologic Oncology, Faculty of Health Sciences, Nicolaus Copernicus University, Collegium Medicum, 85-796 Bydgoszcz, Poland
2
Department of Neurosurgery, Military Clinical Hospital, 85-681 Bydgoszcz, Poland
3
Outpatient Chemiotherapy The F. Lukaszczyk Oncology Center, 85-796 Bydgoszcz, Poland
4
Department of Pathomorphology, Military Clinical Hospital, 85-681 Bydgoszcz, Poland
5
Molecular Oncology and Genetics Department, The F. Lukaszczyk Oncology Center, 85-796 Bydgoszcz, Poland
6
Department of Thoracic Surgery and Tumors, Faculty of Medicine, Nicolaus Copernicus University, Collegium Medicum, 85-796 Bydgoszcz, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 16 September 2016 / Revised: 27 October 2016 / Accepted: 4 November 2016 / Published: 10 November 2016
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [453 KB, uploaded 10 November 2016]   |  

Abstract

The IDH1/2 gene mutations, ATRX loss/mutation, 1p/19q status, and MGMT promoter methylation are increasingly used as prognostic or predictive biomarkers of gliomas. However, the effect of their combination on radiation therapy outcome is discussable. Previously, we demonstrated that the IDH1 c.G395A; p.R132H mutation was associated with longer survival in grade II astrocytoma and GBM (Glioblastoma). Here we analyzed the MGMT promoter methylation status in patients with a known mutation status in codon 132 of IDH1, followed by clinical and genetic data analysis based on the two statuses. After a subtotal tumor resection, the patients were treated using IMRT (Intensity-Modulated Radiation Therapy) with 6 MeV photons. The total dose was: 54 Gy for astrocytoma II, 60 Gy for astrocytoma III, 60 Gy for glioblastoma, 2 Gy per day, with 24 h intervals, five days per week. The patients with MGMT promoter methylation and IDH1 somatic mutation (OS = 40 months) had a better prognosis than those with MGMT methylation alone (OS = 18 months). In patients with astrocytoma anaplasticum (n = 7) with the IDH1 p.R132H mutation and hypermethylated MGMT, the prognosis was particularly favorable (median OS = 47 months). In patients with astrocytoma II meeting the above criteria, the prognosis was also better than in those not meeting those criteria. The IDH1 mutation appears more relevant for the prognosis than MGMT methylation. The IDH1 p.R132H mutation combined with MGMT hypermethylation seems to be the most advantageous for treatment success. Patients not meeting those criteria may require more aggressive treatments. View Full-Text
Keywords: glioma; IDH1; MGMT; radiotherapy; survival glioma; IDH1; MGMT; radiotherapy; survival
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MDPI and ACS Style

Roszkowski, K.; Furtak, J.; Zurawski, B.; Szylberg, T.; Lewandowska, M.A. Potential Role of Methylation Marker in Glioma Supporting Clinical Decisions. Int. J. Mol. Sci. 2016, 17, 1876.

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