Molecular diagnostics of gliomas: state of the art

Riemenschneider, Markus J.; Jeuken, Judith; Wesseling, Pieter; Reifenberger, Guido

doi:10.1007/s00401-010-0736-4

Cited by 246 publications

(221 citation statements)

References 131 publications

(198 reference statements)

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“…LOH and FISH, investigating only a limited numbers of loci on these chromosomes, are often used in such studies and may not allow for a clear identification of tumors with a complete 1p/19q co-deletion as they cannot be accurately distinguished from other types of 1p/19q aberrations. 31 The inclusion of different types of 1p/ 19q aberrations in one group may prohibit identification of the true clinical value for the individual subgroups. 32 Moreover, differences in criteria used to diagnose glioblastoma (vs, eg, anaplastic (oligo)astrocytoma) may have contributed to masking this lack of favorable prognosic impact of 1p/19q co-deletion.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2013

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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;

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Section: Discussionmentioning

confidence: 99%

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

et al. 2013

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“…Currently, the most relevant molecular markers in diagnostics of diffuse gliomas include 1p/19q deletion, MGMT promoter hypermethylation, and IDH1 mutation (Jansen et al, 2010;Riemenschneider et al, 2010;von Deimling et al, 2011). In this study, we have assessed associations between gene copy number changes by array CGH, methylation status of MGMT gene by pyrosequencing and IDH1 mutation status by immunohistochemistry in different glioma subtypes.…”

Section: Discussionmentioning

confidence: 99%

The hypermethylation of the O⁶‐methylguanine‐DNA methyltransferase gene promoter in gliomas—correlation with array comparative genome hybridization results and IDH1 mutation

Tuononen

Tynninen

Sarhadi

et al. 2011

Genes Chromosomes & Cancer

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The use of molecular markers in the diagnostics of gliomas aids histopathological diagnosis and allows their further classification into clinically significant subgroups. The aim of this study was to characterize the methylation pattern of the O 6 -methylguanine-DNA methyltransferase (MGMT) promoter, gene copy number aberrations, and isocitrate dehydrogenase I (IDH1) mutation in gliomas. We studied 51 gliomas (15 oligodendrogliomas, 18 oligoastrocytomas, 3 astrocytomas, and 15 glioblastomas) by pyrosequencing, array comparative genome hybridization (CGH), and immunohistochemistry. MGMT hypermethylation was observed in 100% of oligoastrocytomas, 93% of oligodendrogliomas, and 47% of glioblastomas. The most frequently altered chromosomal regions were deletions of 1p31.1/21.1-22.2 and 19q13.3qter in oligodendroglial tumors, and losses of 9p21.3, 10q25.3qter, and 10q26.13-26.2 in glioblastomas. Deletions on 9p and 10q, and gain of 7p were associated with the unmethylated MGMT phenotype, whereas deletion of 19q and oligodendroglial morphology was associated with MGMT hypermethylation. IDH1 mutation showed positive correlation with MGMT hypermethylation and loss of 1p/19q. Our results suggest that MGMT promoter methylation, analyzed by pyrosequencing, is a frequent event in oligodendroglial tumors, and it correlates with IDH1 mutation and 19q loss in gliomas. Pyrosequencing proved a good method for assessing the degree of MGMT methylation in formalin-fixed paraffin-embedded glioma samples. However, further studies are needed to confirm a clinically relevant cut-off point for MGMT methylation in gliomas.

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“…19 Neuroimaging, in particular MRI, is instrumental for cancer staging and for follow-up after glioma therapy. Blood biomarkers are firmly established for screening and early diagnosis, monitoring therapeutic effects, and predicting recurrence in patients with cancer.…”

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Downregulation of serum microRNA-205 as a potential diagnostic and prognostic biomarker for human glioma

Xiao

Lan

et al. 2016

JNS

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G lioma is the most common primary intracranial tumor in adults, accounting for more than 40% of primary CNS neoplasms. In accordance with WHO classification, which is based on histomorphological criteria, gliomas are categorized as well-differentiated low-grade astrocytoma (WHO Grade I or II), anaplastic astrocytoma (WHO Grade III), or glioblastoma (GBM; WHO Grade IV). 15 The most frequent and malignant glioabbreviatioNs GBM = glioblastoma; KPS = Karnofsky Performance Scale; miR-205 = microRNA 205; miRNA = microRNA; OS = overall survival; PCNSL = primary diffuse large B-cell lymphoma of the CNS; qRT-PCR = quantitative reverse-transcription polymerase chain reaction. obJective Circulating microRNAs (miRNAs) are a new class of highly promising cancer biomarkers. Malignant glioma is one of the most devastating and lethal forms of intrinsic CNS tumor. Here, the authors evaluated serum miRNA 205 (miR-205) levels in patients with glioma. methods Sixty-four patients in whom glioma was diagnosed and 45 healthy controls were recruited between October 2011 and March 2012 and randomly assigned to the screening cohort or the validation cohort. Cohorts of patients with other brain tumors, including meningioma (n = 8), primary diffuse large B-cell lymphoma of the CNS (n = 6), and pituitary adenoma (n = 5), were investigated and compared. miR-205 extraction from serum was detected by real-time quantitative reverse-transcription polymerase chain reaction. The Kaplan-Meier method was applied to perform survival analysis, the risk factors were analyzed by using a Cox regression model, and the receiver operating characteristic working curve was used to analyze the value of miR-205 in the prognostic evaluation of the patients. results The authors first demonstrated that serum miR-205 expression was significantly lower in patients with glioma than in healthy controls (p < 0.001). It is important to note that serum miR-205 expression demonstrated a stepwise decrease with ascending pathological grades. The serum miR-205 biomarker had high sensitivity, specificity, and accuracy in patients with glioma. Serum levels of miR-205 were identified as an individual diagnostic marker and were significantly lower in the glioma cohort than in the other brain tumor cohorts. Serum miR-205 levels were significantly increased in postoperative samples over those in the preoperative samples and were reduced again during glioblastoma recurrences. Statistical analysis revealed a significant correlation between low serum miR-205 expression and both ascending pathological grades (p = 0.002) and low Karnofsky Performance Scale scores (p = 0.01). Patients with glioma at an advanced pathological grade (Grade III or IV) and a higher miR-205 serum level showed longer overall survival than those with a lower miR-205 serum concentration (p < 0.01). Furthermore, Cox regression analysis revealed that miR-205 serum levels were independently associated with overall survival. coNclusioNs These data indicate that serum miR-205 expression is a novel and valuable bioma...

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Molecular diagnostics of gliomas: state of the art

Cited by 246 publications

References 131 publications

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

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

The hypermethylation of the O⁶‐methylguanine‐DNA methyltransferase gene promoter in gliomas—correlation with array comparative genome hybridization results and IDH1 mutation

Downregulation of serum microRNA-205 as a potential diagnostic and prognostic biomarker for human glioma

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Molecular diagnostics of gliomas: state of the art

Cited by 246 publications

References 131 publications

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

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

The hypermethylation of the O6‐methylguanine‐DNA methyltransferase gene promoter in gliomas—correlation with array comparative genome hybridization results and IDH1 mutation

Downregulation of serum microRNA-205 as a potential diagnostic and prognostic biomarker for human glioma

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The hypermethylation of the O⁶‐methylguanine‐DNA methyltransferase gene promoter in gliomas—correlation with array comparative genome hybridization results and IDH1 mutation