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Background: Subependymal giant cell astrocytoma (SEGA) is a World Health Organization grade 1 neoplasm, which, due to its dubious morphologic features, may be misdiagnosed as a high-grade tumor at times. This tumor shows binary immunoexpression including both glial and neural markers, leading to a state of diagnostic quandary. Recent evidences have surmised the diagnostic utility of thyroid transcription factor 1 (TTF-1), spurring us to study the practicality of this marker in distinguishing SEGAs from its mimics., Methods: In this study, TTF-1 immunohistochemistry using clone 8G7G3/1 (1:50) was performed in 38 cases of SEGA, 30 cases of central neurocytoma, 10 cases each of intraventricular glioblastoma and ependymoma, and 5 cases of cortical tubers. Additionally, serine/threonine-protein kinase B-Raf (BRAFV600E) mutation, a common genetic alteration in pediatric low-grade-glial tumors with neuronal-differentiation, was analyzed using Ventana immunohistochemistry platform., Results: TTF-1 immunopositivity was seen in all 38 cases (100%) of SEGAs, with 20 cases (52.6%) showing diffuse (>50% of tumor area) expression while focal (<50%) immunopositivity was seen in 18 cases (47.3%). None of the cases demonstrated serine/threonine-protein kinase B-Raf immunolabeling. Barring 2 cases of neurocytoma (6.6%), all other cases including ependymoma, glioblastoma, and cortical tubers were immunonegative for TTF-1., Conclusions: The congruous finding of TTF-1 expression in SEGA and cells of the developing neuroepithelium in the medial ganglionic eminence hint toward a primogenitor cell with neoplastic potential in the presence of impelling factors., (Published by Elsevier Inc.)

Aim: Glioblastoma (GBM) is one of the most aggressive neoplasms of the central nervous system with dismal survival. In recent years, different variants of GBM have been described in the literature. GBM with areas of neuroectodermal differentiation (GBM-PNET) is a relatively new entity in GBM. Presence of the neuroectodermal component increases the propensity of systemic dissemination as with other intracranial primitive neuroectodermal tumors (PNET). The optimal treatment for these patients remains a controversy, with authors reporting local radiotherapy to craniospinal irradiation and chemotherapy. We intend to analyze the pattern of care for GBM with neuroectodermal component., Materials and Methods: We retrieved data of four patients with GBM-PNET treated in our institute; data were also retrieved from published series to derive treatment and outcome results., Results: In this series, we report the outcome of a series of four patients of GBM-PNET treated with adjuvant radiotherapy and temozolomide. All but one patient underwent gross total resection of the tumor. Adjuvant hypofractionated radiation with concurrent and adjuvant temozolomide was used in all cases. The median follow-up was 12.9 months in the present series. One patient experienced local recurrence 18 months after the treatment. A review of published literature on GBM-PNET was done; studies with details of patient outcome were used for an independent analysis. Twenty-three patients were identified, and the pooled analysis revealed a median progression free and overall survival of 10 and 25, months respectively. Extent of surgery, local radiation vs. craniospinal irradiation, and age at presentation had no impact on the survival., Conclusion: GBM PNET is a new entity with only few cases reported so far. Clinical behavior and treatment outcome of these tumors are not different from conventional GBM. However, these patients are at higher risk of CSF dissemination. Hence, an individualized treatment approach is best suited., Competing Interests: None

Epithelioid glioblastoma (e-gbm) is a recently described variant of glioblastoma (GBM) which is associated with short survival and now added as a provisional entity to WHO 2016 classification of CNStumors. About half of these tumors show characteristic BRAF-V600E mutation. However, unlike conventional GBMs, e-gbm lack specific diagnostic and prognostic markers. Hence, we aimed to molecularly characterize these tumors. An extensive review of literature was performed.In a multi-institutional effort, all the cases of glioblastoma of year 2017 were reviewed. Cases with predominant epithelioid morphology were analysed. Seven cases of e-gbm (adults:4 and pediatric: 3) were identified. Duration of symptoms varied from 2 weeks to one month. Radiologically, all cases were supratentorial, contrast enhancing with solid and cystic appearance. Majority of the cases were immunopositive for GFAP (71%), EMA (71%), S100 (71%) and vimentin (85%). All the cases showed ATRX, INI-1 and H3K27me3 expression. BRAFV600Emutation was seen in 28% of cases. TERT mutation was seen in 40% cases, while one case showed EGFR amplification. H3F3A mutations and PTEN deletions were seen in none. Although e-gbms are rare, epithelioid morphology of a CNS tumor in a young adult or children with areas of necrosis needs thorough histomorphological and genetic workup., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Enhancer of zeste homolog-2(EZH2) is a key epigenetic regulator that functions as oncogene and also known for inducing altered trimethylation of histone at lysine-27 (H3K27me3) mark in various tumors. However, H3K27me3 targets and their precise relationship with gene expression are largely unknown in astrocytic tumors. In this study, we checked EZH2 messenger RNA and protein expression in 90 astrocytic tumors of different grades using quantitative PCR and immunohistochemistry, respectively. Further, genome-wide ChIP-seq analysis for H3K27me3 modification was also performed on 11 glioblastomas (GBMs) and 2 diffuse astrocytoma (DA) samples. Our results showed EZH2 to be highly overexpressed in astrocytic tumors with a significant positive correlation with grade. Interestingly, ChIP-seq mapping revealed distinct differences in genes and pathways targeted by these H3K27me3 modifications between GBM versus DA. Neuroactive ligand receptor pathway was found most enriched in GBM (P = 9.4 × 10-25), whereas DA were found to be enriched in metabolic pathways. Also, GBM showed a higher enrichment of H3K27me3 targets reported in embryonic stem cells and glioma stem cells as compared with DAs. Our results show majority of these H3K27me3 target genes were downregulated, not only due to H3K27me3 modification but also due to concomitant DNA methylation. Further, H3K27me3 modification-associated gene silencing was not restricted to promoter but also present in gene body and transcription start site regions. To the best of our knowledge, this is the first high-resolution genome-wide mapping of H3K27me3 modification in adult astrocytic primary tissue samples of human, highlighting the differences between grades. Interestingly, we identified SLC25A23 as important target of H3K27me3 modification, which was downregulated in GBM and its low expression was associated with poor prognosis in GBMs., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

This study aims to analyze expression of EZH2 and DNA-methyltransferases (DNMT1, 3A and 3B) in astrocytic tumors and investigate their link as well as their correlation with survival, especially in GBMs. Expression of EZH2 and DNMTs (DNMT1, DNMT3A and DNMT3B) in different grades of astrocytomas (n=93) was assessed by qRT-PCR and immunohistochemistry. GBM-U87MG cell line was used for functional studies. Strong immunopositivity (LI≥25%) for EZH2, DNMT1 and DNMT3B was detected in 52%, 56% and 64% cases of GBMs respectively, which was significantly higher as compared to Grade II/III cases. Similarly, their median fold change of mRNA expression was also significantly higher in GBMs. There was also a significant positive correlation between DNMT1/DNMT3B and EZH2 mRNA and protein expression, which was in concordance with TCGA data set. Inhibition of DNMTs in cell line by Azacytidine resulted in down-regulation of EZH2, while knock-down of EZH2 by siRNA was not associated with any significant alteration of DNMTs, indicating that EZH2 expression in GBMs is possibly regulated by DNMTs, but not the reverse. Strong immunopositivity for EZH2, DNMT1 and DNMT3B were individually associated with significantly shorter survival and showed no correlation with IDH1 mutation status. In addition, the combination of these 3 markers represented an independent prognostic signature with cases having weak/negative expression of all 3 markers being associated with best prognosis. For the first time, the present study describes an epigenetic prognostic signature in GBMs based on immunohistochemical expression of EZH2, DNMT1 and 3B which can be used easily in routine neuropathology practice., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Pediatric glioblastoma multiforme (GBM) is rare, and there is a single study, a seminal discovery showing association of histone H3.3 and isocitrate dehydrogenase (IDH)1 mutation with a DNA methylation signature. The present study aims to validate these findings in an independent cohort of pediatric GBM, compare it with adult GBM, and evaluate the involvement of important functionally altered pathways., Methods: Genome-wide methylation profiling of 21 pediatric GBM cases was done and compared with adult GBM data (GSE22867). We performed gene mutation analysis of IDH1 and H3 histone family 3A (H3F3A), status evaluation of glioma cytosine-phosphate-guanine island methylator phenotype (G-CIMP), and Gene Ontology analysis. Experimental evaluation of reactive oxygen species (ROS) association was also done., Results: Distinct differences were noted between methylomes of pediatric and adult GBM. Pediatric GBM was characterized by 94 hypermethylated and 1206 hypomethylated cytosine-phosphate-guanine (CpG) islands, with 3 distinct clusters, having a trend to prognostic correlation. Interestingly, none of the pediatric GBM cases showed G-CIMP/IDH1 mutation. Gene Ontology analysis identified ROS association in pediatric GBM, which was experimentally validated. H3F3A mutants (36.4%; all K27M) harbored distinct methylomes and showed enrichment of processes related to neuronal development, differentiation, and cell-fate commitment., Conclusions: Our study confirms that pediatric GBM has a distinct methylome compared with that of adults. Presence of distinct clusters and an H3F3A mutation-specific methylome indicate existence of epigenetic subgroups within pediatric GBM. Absence of IDH1/G-CIMP status further indicates that findings in adult GBM cannot be simply extrapolated to pediatric GBM and that there is a strong need for identification of separate prognostic markers. A possible role of ROS in pediatric GBM pathogenesis is demonstrated for the first time and needs further evaluation., (© The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cell cycle regulator genes are major target of mutation in many human malignancies including glioblastomas (GBMs). CDKN2A is one such tumor suppressor gene which encodes p16INK4a protein and serves as an inhibitor of cell cycle progression. Very few studies are available regarding the association of CDKN2A deletion with p16 protein expression in GBMs. There is limited data on the frequency of CDKN2A deletion in different age groups. The aim of the present study was to analyze the frequency of CDKN2A gene deletions in GBM and correlate CDKN2A deletional status with (i) age of the patient (ii) p16 protein expression and (iii) other genetic alterations, namely EGFR amplification and TP53 mutation. A combined retrospective and prospective study was conducted. Sixty seven cases were included. The patients were grouped into pediatric (≤ 18 years), young adults (19-40 years) and older adults (>40 years). CDKN2A and EGFR status were assessed by Fluorescence in situ Hybridization.TP53 mutation was analyzed by PCR based method. p16 expression was assessed using immunohistochemistry. CDKN2A deletion was noted in 40.3% cases of GBM with majority being homozygous deletion (74%). It was commoner in primary GBMs (65.8%) and cases with EGFR amplification (50%). A variable frequency of CDKN2A was observed in older adults (42.3%), young adults (44%), and pediatric patients (31.25%). The difference however was not statistically significant. There was statistically significant association between CDKN2A deletion and p16 immunonegativity with a high negative predictive value of immunohistochemistry., (© 2013 Japanese Society of Neuropathology.)

To evaluate age-related differences in histopathologic and molecular profile of glioblastomas (GBMs) at various age groups, with special reference to TP53 mutation, epidermal growth factor receptor (EGFR) amplification, EGFR vIII mutant, PTEN deletion, and IDH1 mutation. Agewise GBM incidence was calculated over a period of 5 years (2005 to 2009). Seventy-five GBMs were selected for molecular analysis. Majority of cases were in the age group of 41 to 60 years, and mean age was 43.6 years. Histology of all 75 cases selected for molecular profiling was identical. Primary adult GBMs showed EGFR amplification and PTEN deletion in majority (37.3% and 54.9%, respectively). TP53 and IDH1 mutations were rare (11.8% cases each). In secondary GBMs, TP53 (66.7%) and IDH1 mutations (44.4%) were most frequent. PTEN deletion was seen in 33.3% and none had EGFR amplification. Pediatric GBMs (<18 y) harbored frequent TP53 mutations (46.7%) and PTEN deletion in 40%. IDH1 mutations and EGFR amplification were absent. The molecular profile of primary GBMs in young adults (19 to 40 y) was distinctly different from that of adults older than 40 years. TP53 mutation was present in 20% cases. The frequency of EGFR amplification (13.3%) and PTEN deletion (33.3%) was significantly low (P=0.028 and 0.046, respectively). IDH1 mutation, which is rare in primary adult GBMs, was present in 40% of cases. Molecular heterogeneity exists within GBMs of different age cohorts. The molecular profile of GBMs in young adults is distinctly different. Thus, there is a strong need for further studies in various age groups to provide guidelines for therapeutic targeting.

Combined loss of chromosome arms 1p and 19q in oligodendroglial tumors has become a powerful predictor of prognosis and treatment response, and hence clinical testing for their detection is widely used nowadays. Polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) analysis and fluorescence in-situ hybridization (FISH) are the 2 important relatively common clinical molecular diagnostic techniques used for this purpose and they have their unique advantages and limitations. The preference of methodology used depends on local expertise and existing laboratory capabilities. However, there is no consensus on which methodologic approach has a better potential. The objective of the study was to compare the accuracy, reliability, and feasibility of FISH and PCR in detecting the 1p and 19q LOH status. Using the PCR-based method, a LOH analysis was performed on 30 oligodendrogliomas and 10 glioblastomas using fresh-frozen tissue and peripheral blood as control. A FISH assay using paraffin blocks was performed on all the cases. Concordance for 1p and 19q was found in 92.5% (37 of 40) and 82.5% (33 of 40) cases, respectively. The relative advantages and limitations of both the techniques are analyzed and discussed. The main issue pertains to the use of the best technique in large clinical trials whose results are translated to patient care services. Unless the technique used is correct, the results of clinical trials and their correlations may be somewhat questionable.

Background: Glioblastoma multiforme (GBM) is the most common malignant central nervous system neoplasm. Loss of heterozygosity (LOH) on chromosome 10q in these tumors has been found to show variable association with prognosis., Aim: To evaluate LOH 10q status in cases of GBM, and to correlate these results with patient characteristics, other genetic alterations, and survival., Material and Methods: Fresh tumor tissue and blood samples were obtained for 25 cases of GBM diagnosed over a 2-year period. LOH 10q assay was performed on blood and tumor DNA by a PCR-based method using four microsatellite markers. TP53 mutation analysis and fluorescence in situ hybridization for epidermal growth factor receptor (EGFR) were performed. Histopathology was reviewed and clinical data were analyzed., Results: LOH 10q was identified in 17 of 25 cases (68%). Losses were frequent with markers D10S1765 (12/20 informative cases; 60%) and D10S587 (12/17 informative cases; 70.5%) in the regions of 10q23.3 and 10q26.1, respectively. D10S540 for 10q25.1 showed LOH in 4/12 informative cases (33.3%) and D10S1770 for 10q26-ter in none of the 25 cases. LOH with D10S1765 at the PTEN gene locus was found to correlate with overall LOH 10q status (P = 0.001). LOH 10q was more common in patients older than 40 years (16/19, 84.2%) than in those below (1/6, 16.7%) (P = 0.006). One of three pediatric patients included demonstrated LOH 10q. Survival rates for patients with LOH were lower than for patients with retained heterozygosity., Conclusion: LOH 10q is a frequent genetic abnormality in GBM in Indian patients, is seen more frequently in older adults, and its presence is associated with shorter survival. The single best marker to determine LOH 10q status is D10S1765 at the PTEN region.

The median survival time of patients with glioblastoma multiforme (GBM) is 12 months, and only 3-5% of patients survive longer than 3 years. We performed histomorphological and detailed molecular analyses of seven long-term survivors of GBM to identify any prognostic factors that potentially contribute to survival. Morphology and immunohistochemistry for p53, phosphatase and tensin homologue (PTEN) and epidermal growth factor receptor (EGFR) protein expression were investigated. EGFR amplification and 1p/19q deletion were assessed by fluorescent in situ hybridization. The O6-methylguanine-DNA methyltransferase (MGMT) gene methylation status was evaluated by performing methylation-specific polymerase chain reaction assays. All tumors were classical GBMs and no significant oligodendroglial differentiation was noted. The majority showed EGFR amplification (4/7), PTEN protein expression (6/7) and MGMT promoter methylation (5/6). Immunopositivity for p53 was noted in three of seven patients. Deletion of chromosome 1p/19q, either isolated or combined, was not identified in any of the se patients. All patients were treated by gross total resection followed by radiotherapy; six patients received additional temozolomide treatment. A relatively young age of onset (48 years), with a high MGMT promoter methylation and PTEN protein expression were favorable factors for long-term survival. The presence of EGFR amplification indicates that more than a single factor determines survival in GBM., (2010 Elsevier Ltd. All rights reserved.)

Purpose: Relatively few studies have been performed on molecular properties of pediatric glioblastoma multiforme (GBM). Methylation of DNA repair gene O(6)-methylguanine-DNA methyltransferase (MGMT) promoter region has been associated with favorable prognosis and prolonged survival in adult GBM patients treated with temozolomide (TMZ). We explored the frequency of MGMT gene promoter methylation in pediatric glioblastomas and compared it with the known molecular alterations in p53., Methods: Twenty pediatric GBM cases were selected. MGMT promoter methylation was assessed by methylation specific PCR. p53 expression was determined by immunohistochemistry., Results: MGMT gene promoter methylation was observed in 50% of pediatric glioblastomas. p53 protein expression was detected in 60% of cases. Seventy percent of cases with methylated MGMT promoter were p53 immunopositive., Conclusions: The frequency of MGMT gene promoter methylation in pediatric GBMs was similar to adult GBM patients. The pediatric GBMs should also be investigated for MGMT promoter methylation to identify a subset of patients likely to benefit from TMZ therapy. p53 protein overexpression was more common in pediatric primary GBMs. To the best of our knowledge this is only the second study on MGMT gene promoter methylation status in pediatric GBMs.

Glioblastoma multiforme (GBM) occurs rarely in children. Relatively few studies have been performed on molecular properties of pediatric GBMs. Our objective in this study was to evaluate the genetic alterations in pediatric GBM (age < or = 18 years) with special reference to p53, p16, and p27 protein expression, alterations of the epidermal growth factor receptor (EGFR), and deletion of the phosphate and tensin homolog gene (PTEN). Thirty cases of childhood GBMs reported between January 2002 and June 2007 were selected, and slides stained with hematoxylin and eosin were reviewed. Immunohistochemical staining was performed for EGFR, p53, p16, and p27, and tumor proliferation was assessed by calculating the MIB-1 labeling index (LI). Fluorescence in situ hybridization analysis was performed to evaluate for EGFR amplification and PTEN deletion. Histopathological features and MIB-1 LI were similar to adult GBMs. p53 protein expression was observed in 63%. Although EGFR protein overexpression was noted in 23% of cases, corresponding amplification of the EGFR gene was rare (5.5%). Deletion of the PTEN gene was also equally rare (5.5%). One case showed polysomy (chromosomal gains) of chromosomes 7 and 10. Loss of p16 and p27 immunoexpression was observed in 68% and 54% of cases, respectively. In pediatric de novo/primary GBMs, deletion of PTEN and EGFR amplification are rare, while p53 alterations are more frequent compared to primary adult GBMs. Frequency of loss of p16 and p27 immunoexpression is similar to their adult counterparts. This suggests that pediatric malignant gliomas are distinctly different from adult GBMs, highlighting the need for identification of molecular targets that may be adopted for future novel therapeutic strategies.

Introduction: Giant cell glioblastomas (GCGs) and gliosarcomas are rare histological variants of glioblastoma multiforme (GBMs). The mean age of occurrence in GCG is 42 years, but occasional cases have been documented in children under 10 years of age. Clinically, they are associated with a better prognosis than conventional GBMs, with few reports documenting prolonged survival up to 17 years after diagnosis. In contrast, gliosarcomas have age distribution and survival characteristics similar to conventional GBMs. They either arise de novo (primary) or secondary to irradiation to GBM., Case Report: We report a rare case of childhood GCG in an 8-year-old boy surviving for more than 10 years since initial diagnosis. He has had two recurrences at the ages of 16 and 17 years, respectively, with histopathology at second recurrence showing evidence of gliosarcoma., Discussion: No such case of gliosarcoma following treatment for GCG has been reported in the literature. Hence, the origin of the gliosarcoma whether radiation induced or only a phenotypic change in the GBM remains conjectural.

Glioblastoma multiforme (GBM) Patients generally have a dismal prognosis, with median survival of 10-12 months. GBM with long-term survival (LTS) of (3) > or = 5 years is rare, and no definite markers indicating better prognosis have been identified till date. The present study was undertaken to evaluate GBMs with LTS in order to identify additional correlates associated with favourable outcome. The cases were evaluated for relevant clinicopathological data, proliferation index and expression of tumortumour suppressor gene (p53 ), cyclin-dependant kinase-inhibitors (p27 and p16 ) and epidermal growth factor receptor (EGFR) proteins. Six cases of GBM with LTS with an average survival of 9 years (range 5-15 years) were identified. All were young patients with mean age of 27 years (range 8-45 years). Histology of three cases was consistent with conventional GBM, while two showed prominent oligodendroglial component admixed with GBM areas. One was a giant cell GBM, which progressed to gliosarcoma on recurrence. The mean MIB-1LI was 12% (range 6-20%). p53 was immunopositive in 4 out of 5 cases. EGFR and p27 were immunonegative in all, whereas p16 was immunonegative in 3 out of 5 cases. Currently, in the absence of specific molecular and genetic markers, GBM in young patients should be meticulously evaluated for foci of oligodendroglial component and/or giant cell elements, in addition to proliferative index and p53 expression, since these probably have prognostic connotations, as evident in this study. The role of p16 and p27 however needs better definition with study of more number of cases.

Apoptosis and cell proliferation occur simultaneously in tumour tissue with tumour suppressor gene, p53 being one of the key players in the complex relationship between these two key phenomena. We, as well as several other groups, have earlier demonstrated the association of p53 immunopositivity with increased degree of cell proliferation in astrocytic tumours. Here we have studied the extent of apoptosis in 62 primary human astrocytic tumours [25 Diffuse Astrocytoma (DA), 9 Anaplastic Astrocytoma (AA) and 28 Glioblastoma multiforme (GBM)] in relation to tumour grade, proliferative status and p53 protein expression. Apoptosis was measured by the TUNEL assay while, cell proliferation (MIB-1 index) and p53 protein immunoreactivity were evaluated by immunohistochemical staining using MIB-1 and DO-1 monoclonal antibodies respectively. The apoptotic index (AI) was greater in GBM than in AA or DA, and more in tumours with p53 immunopositivity than in those without. The most striking observation was the strong correlation between Apoptotic index (AI) and proliferation index (PI) in p53 negative GBM (r=0.766, P < 0.005). However this was not observed in p53 +ve GBM or in low grade DA either p53 positive or negative. Taking p53 negativity in IHC as evidence of a functional gene/protein, this extends the link between proliferation and apoptosis, hitherto observed only in cultured cells with functional p53, to a subset of solid tumours.

The concept of different genetic pathways leading to glioblastoma multiforme (GBM) has gained considerable acceptance, and two major groups are now described, primary or de novo GBM and secondary GBM. The present study was undertaken to elucidate whether additional pathways exist and to determine whether there is any correlation between these different variants and clinical parameters, such as age, duration of symptoms, and outcome. For this purpose, immunophenotyping was performed to study the simultaneous expression of p53 protein and epidermal growth factor receptor (EGFR) in 58 cases of adult supratentorial GBM. By this method, four variants of GBM could be distinguished: 34% were p53 positive only, 38% were EGFR positive only, 14% were double negative (p53 negative/EGFR negative), and 14% were double positive (p53 positive/EGFR positive). Interestingly, all nine cases of secondary GBM in which there was clinical and histological evidence of progression from a preexisting low-grade lesion were p53 positive. Differences were observed with regard to the age distribution of the four variants, in that the p53 negative/EGFR negative tumors occurred most frequently in the younger age group (21-40 years). In the elderly group (61-80 years), two-thirds of the tumors were p53 negative/EGFR positive primary GBMs, and no case of the double positive or double negative variant was encountered. The differences in duration of symptoms and symptom-free survival according to age group and genetic subset were not statistically significant. There were no differences in outcome within each age category for any GBM variant, although the longest mean symptom-free survival was noted among patients aged 41-60 years with the p53 positive/EGFR negative variant. This study therefore indicates that at least four subsets of GBM exist, but despite different genotypes, the biologic behavior remains similar. Other genetic alterations therefore need to be investigated to identify prognostic makers.

Assessment of promoter methylation of the O6-methylguanine DNA methyltransferase (MGMT) gene has recently gained importance in molecular profiling of high-grade gliomas. It has emerged not only as an important prognostic marker but also as a predictive marker for response to temozolomide in patients with newly diagnosed glioblastoma. Further, recent studies indicate that MGMT promoter methylation has strong prognostic relevance even in anaplastic (grade III) gliomas, irrespective of therapy (chemotherapy or radiotherapy). This article provides an overview of its use as a predictive and prognostic biomarker, as well as the methods employed for its assessment and use in therapeutic decision making. [ABSTRACT FROM AUTHOR]