Potential Role of Methylation Marker in Glioma Supporting Clinical Decisions.
TheIDH1/2 gene mutations,ATRXloss/mutation, 1p/19q status, andMGMTpromoter 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 theIDH1c.G395A; p.R132H mutation was associated with longer survival in grade II astrocytoma and GBM (Glioblastoma). Here we analyzed theMGMTpromoter methylation status in patients with a known mutation status in codon 132 ofIDH1, 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 withMGMTpromoter methylation andIDH1somatic mutation (OS = 40 months) had a better prognosis than those withMGMTmethylation alone (OS = 18 months). In patients with astrocytoma anaplasticum (n= 7) with theIDH1p.R132H mutation and hypermethylatedMGMT, 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. TheIDH1mutation appears more relevant for the prognosis thanMGMTmethylation. TheIDH1p.R132H mutation combined withMGMThypermethylation seems to be the most advantageous for treatment success. Patients not meeting those criteria may require more aggressive treatments.
Department of Oncology, Radiotherapy and Ginecologic Oncology, Faculty of Health Sciences, Nicolaus Copernicus University, Collegium Medicum, 85-796 Bydgoszcz, Poland. roszkowskik@cm.umk.pl.
Krzysztof
K
Roszkowski
Department of Neurosurgery, Military Clinical Hospital, 85-681 Bydgoszcz, Poland. jacekf67@poczta.onet.pl.
Jacek
J
Furtak
Outpatient Chemiotherapy The F. Lukaszczyk Oncology Center, 85-796 Bydgoszcz, Poland. bzur@wp.pl.
Bogdan
B
Zurawski
Department of Pathomorphology, Military Clinical Hospital, 85-681 Bydgoszcz, Poland. szylberg@10wsk.mil.pl.
Tadeusz
T
Szylberg
Molecular Oncology and Genetics Department, The F. Lukaszczyk Oncology Center, 85-796 Bydgoszcz, Poland. lewandowskam@co.bydgoszcz.pl.|Department of Thoracic Surgery and Tumors, Faculty of Medicine, Nicolaus Copernicus University, Collegium Medicum, 85-796 Bydgoszcz, Poland. lewandowskam@co.bydgoszcz.pl.
Marzena A
MA
Lewandowska
D000328:Adult; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000532:radiotherapy*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D025521:Tumor Suppressor Proteins; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
IDH1; MGMT; glioma; radiotherapy; survival