Promoter methylation of RB1, P15, P16, and MGMT and their impact on the clinical course of pilocytic astrocytomas

Sippl, Christoph; Urbschat, Steffi; Kim, Yoo Jin; Senger, Sebastian; Oertel, Joachim; Ketter, Ralf

doi:10.3892/ol.2017.7490

Cited by 8 publications

(8 citation statements)

References 38 publications

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“…MGMT was determined by methylation-specific polymerase chain reaction (MS-PCR), as described previously [33]. Immunohistochemistry for IDH1 mutation was conducted, as described previously [11].…”

Section: Methylation Analysis and Idh1-r123h Stainingmentioning

confidence: 99%

Impact of MiRNA-181a2 on the Clinical Course of IDH1 Wild Type Glioblastoma

et al. 2021

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Background: Recently, miRNA-181a2 could be identified as a major regulator of IDH1 expression in fat tissue. The IDH1 gene, its mutation and expression have a major impact on overall survival in patients with glioblastoma. The presented study aimed to investigate the effect of miRNA-181a2 on IDH1 expression in glioblastoma and on the prognosis of patients suffering from, for example, a tumor. Methods: A total of 74 glioblastoma specimens were analyzed for the expression of miRNA-181a2, acquired as fold change, using qRT-PCR. IDH1 protein expression was estimated via mRNA quantification. Eight post mortal, non-glioma related brain tissue specimens served as the control group. The results were correlated with relevant demographic and clinical aspects of the cohort. A TCGA dataset was used as an independent reference. Results: MiRNA-181a2 was significantly downregulated in tumor samples compared to the control group (p < 0.001). In the glioblastoma cohort, 63/74 (85.1%) showed an IDH1 wild type, while 11/74 (14.9%) patients harbored an IDH 1 mutation. In patients with IDH1 wild type glioblastoma, low miRNA-181a2 expression correlated with a prolonged overall survival (p = 0.019), also verifiable in an independent TCGA dataset. This correlation could not be identified for patients with an IDH1 mutation. MiRNA-181a2 expression tended to correlate inversely with IDH1 protein expression (p = 0.06). Gross total resection of the tumor was an independent marker for a prolonged survival (p = 0.03). Conclusion: MiRNA-181a2 seems to be a promising prognostic marker of selective glioblastoma patients with IDH1 wild type characteristics. This effect may be mediated via direct regulation of IDH1 expression.

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Section: Methylation Analysis and Idh1-r123h Stainingmentioning

confidence: 99%

Impact of MiRNA-181a2 on the Clinical Course of IDH1 Wild Type Glioblastoma

et al. 2021

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“…In search of novel prognostic factors in adult PAs, we, therefore, focused on MGMT promoter methylation status based on preliminary data derived from a small study of pediatric and adult PAs conducted by Sippl et al [17]. MGMT promoter methylation was present in 8/18 patients (44.5%) and was associated with a higher rate of recurrence and shorter PFS.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, in order to keep diagnostic uncertainty caused by retrospective patient identification to a minimum, all cases underwent neuropathology review and the EOR was quantified objectively by postoperative MRI rather than by the subjective impression of surgical reports. Given the rarity of adult PAs, we analyzed a considerable number of patients and incorporated, in contrast to all but two series [12,17], molecular data into outcome analysis. Naturally, the optimal treatment and robust algorithms for risk stratification should be determined by prospective trials.…”

Section: Discussionmentioning

confidence: 99%

“…However, their prognostic relevance is still unclear. At the epigenetic level, promoter hypermethylation of distinct genes, amongst others, O-6-methylguanine-DNA methyltransferase (MGMT), has recently been suggested as a potential negative prognostic factor in a series of 18 PAs, including six adult patients [17], but requires further validation.…”

Section: Introductionmentioning

confidence: 99%

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Extent of Resection, MGMT Promoter Methylation Status and Tumor Location Independently Predict Progression-Free Survival in Adult Sporadic Pilocytic Astrocytoma

Jungk

Reinhardt

Warta

et al. 2019

Cancers

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In adults, pilocytic astrocytomas (PA) account for less than 2% of gliomas, resulting in uncertainty regarding the clinical course and optimal treatment, particularly in cases where gross total resection (GTR) could not be achieved. Moreover, information on molecular markers and their prognostic impact is sparse. In order to improve risk stratification, we analyzed our institutional series of 58 patients aged 17 years and older with histology-proven intracranial PA World Health Organization grade I for clinical and molecular prognosticators. Anaplastic and NF1-associated tumors were excluded. O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was determined by pyrosequencing or 450k/850k DNA methylation array. A univariate log-rank test and multivariate StepAIC were applied to identify prognostic factors. The median age was 30 years (range 17–66). Tumors were located in the cerebral/cerebellar hemispheres, midline structures and cerebello-pontine angle in 53%, 38% and 9%. MGMT promoter methylation was present in eight patients (14%). GTR (39/58 patients) significantly reduced the likelihood of tumor recurrence (p = 0.0001). Tumor relapse occurred in 16 patients (28%) after a median progression-free survival (PFS) of 135 months (range 6–153 months); there was one tumor-related death. PFS at 5 and 10 years was 67% and 53%. In multivariate analysis, PFS was significantly prolonged in patients with GTR (HR 0.1; CI 0.03–0.37; p < 0.001), unmethylated MGMT promoter (HR 0.18; CI 0.05–0.64; p = 0.009) and midline tumors (HR 0.21; CI 0.06–0.78; p = 0.02). In conclusion, MGMT promoter methylation status and tumor location were identified as novel prognostic factors in adult PAs, pointing at distinct molecular subtypes and detecting patients in need of close observance and intensified treatment.

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“…,Schmidt et al (1994),Ranjit et al (2015),Urbschat et al (2017),Sippl et al (2018),Cerchietti and Melnick (2017) andHe et al Frequently detected in glioma tumors • Monosomy 10 is characteristically related with a more malignant histologic type • The incidence range of chromosome 10 loss in glioblastoma tumors in different studies is from 60% to more than 90% of the cases • Primary glioblastomas are characterized by loss of heterozygosity on entire chromosome 10, while secondary glioblastomas often illustrate LOH on chromosome 10q.…”

mentioning

confidence: 99%

Genetic and epigenetic contribution to astrocytic gliomas pathogenesis

Khani

Nasri

Chamani

et al. 2018

Journal of Neurochemistry

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Astrocytic gliomas are the most common and lethal form of intracranial tumors. These tumors are characterized by a significant heterogeneity in terms of cytopathological, transcriptional, and (epi)genomic features. This heterogeneity has made these cancers one of the most challenging types of cancers to study and treat. To uncover these complexities and to have better understanding of the disease initiation and progression, identification, and characterization of underlying cellular and molecular pathways related to (epi)genetics of astrocytic gliomas is crucial. Here, we discuss and summarize molecular and (epi)genetic mechanisms that provide clues as to the pathogenesis of astrocytic gliomas.

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Promoter methylation of RB1, P15, P16, and MGMT and their impact on the clinical course of pilocytic astrocytomas

Cited by 8 publications

References 38 publications

Impact of MiRNA-181a2 on the Clinical Course of IDH1 Wild Type Glioblastoma

Impact of MiRNA-181a2 on the Clinical Course of IDH1 Wild Type Glioblastoma

Extent of Resection, MGMT Promoter Methylation Status and Tumor Location Independently Predict Progression-Free Survival in Adult Sporadic Pilocytic Astrocytoma

Genetic and epigenetic contribution to astrocytic gliomas pathogenesis

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