Significance of complete 1p/19q co-deletion, IDH1 mutation and MGMT promoter methylation in gliomas: use with caution

Abstract

The histopathological diagnosis of diffuse gliomas often lacks the precision that is needed for tailored treatment of individual patients. Assessment of the molecular aberrations will probably allow more robust and prognostically relevant classification of these tumors. Markers that have gained a lot of interest in this respect are co-deletion of complete chromosome arms 1p and 19q, (hyper)methylation of the MGMT promoter and IDH1 mutations. The aim of this study was to assess the prognostic significance of complete 1p/19q co-deletion, MGMT promoter methylation and IDH1 mutations in patients suffering from diffuse gliomas. The presence of these molecular aberrations was investigated in a series of 561 diffuse astrocytic and oligodendroglial tumors (low grade n ¼ 110, anaplastic n ¼ 118 and glioblastoma n ¼ 333) and correlated with age at diagnosis and overall survival. Complete 1p/19q co-deletion, MGMT promoter methylation and/or IDH1 mutation generally signified a better prognosis for patients with a diffuse glioma including glioblastoma. However, in all 10 patients with a histopathological diagnosis of glioblastoma included in this study complete 1p/19q co-deletion was not associated with improved survival. Furthermore, in glioblastoma patients 450 years of age the favorable prognostic significance of IDH1 mutation and MGMT promoter methylation was absent. In conclusion, molecular diagnostics is a powerful tool to obtain prognostically relevant information for glioma patients. However, for individual patients the molecular information should be interpreted with caution and weighed in the context of parameters such as age and histopathological diagnosis. Modern Pathology (2013) 26, 922-929;

A practical review of prognostic correlations of molecular biomarkers in glioblastoma

“…Results from the Radiation Therapy Oncology Group (RTOG) 9402 and EORTC 26951 trials showed an improvement in OS with the addition of radiation to procarbazine/lomustine/vincristine chemotherapy in anaplastic oligodendroglioma with the 1p/19q mutation. 6 In GBM, similar findings have been demonstrated in some studies 4,21,43,44 but not in others. 13,16,30 In several studies, codeletion of 1p and 19q is associated with IDH1 mutation and MGMT hypermethylation.…”

“…13,16,30 In several studies, codeletion of 1p and 19q is associated with IDH1 mutation and MGMT hypermethylation. 4,44 Nevertheless, in a study of 491 gliomas, 28 patients with GBM showed codeletion of 1p/19q, which did not change OS. 9 Interestingly, 1p/19q mutation was independent of IDH1 mutation, 10q loss, and EGFR alterations.…”

Critical Molecular and Genetic Markers in Primary Brain Tumors with Their Clinical Importance

“…Data obtained from EORTC 26951 and RTOG 9402 trials showed an improvement in OS with the addition of radiation to procarbazine/lomustine/vincristine chemotherapy in anaplastic oligodendroglioma with 1p/19q mutation [50]. There are some studies correlated with these similar findings, In GBM, similar findings have been demonstrated in some studies [51,52], but not in others [53,54]. It has also been reported that codeletion of 1p and 19q is related with IDH1 mutation and MGMT hypermethylation [47,55].…”

Association of loss of heterozygosity with shorter survival in primary glioblastoma patients

“…However, recent data showed that the prognostic significance of these markers should be used with caution [7].…”