Extent, pattern, and prognostic value of MGMT promotor methylation: does it differ between glioblastoma and IDH-wildtype/TERT-mutated astrocytoma?

Teske, Nico; Karschnia, Philipp; Weller, Jonathan; Siller, Sebastian; Dorostkar, Mario M.; Herms, Jochen; Baumgarten, Louisa von; Tonn, Joerg C.; Thon, Niklas

doi:10.1007/s11060-021-03912-6

Cited by 7 publications

(5 citation statements)

References 28 publications

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“…Studies have shown that transcriptional reactivation of TERT is associated with methylation and mutation of its promoter region in a variety of human tumor diseases [34][35][36][37]. However, there is no relevant research demonstrating the difference in the methylation level of chTERT in the promoter region of ALV-J-induced tumors, nor whether there are mutations in the promoter region or the characteristics of the mutations.…”

Section: Discussionmentioning

confidence: 99%

The expression level of chicken telomerase reverse transcriptase in tumors induced by ALV-J is positively correlated with methylation and mutation of its promoter region

Xiang

Chen

et al. 2022

Vet Res

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Avian leukosis virus subgroup J (ALV-J) can cause neoplastic diseases in poultry and is still widely prevalent in China. Chicken telomerase reverse transcriptase (chTERT) is the core component of telomerase, which is closely related to the occurrence and development of tumors. Our previous studies showed that chTERT is overexpressed in ALV-J tumors, but the mechanism is still not completely clear. Therefore, this study aims to analyze the possible molecular mechanism of chTERT overexpression in ALV-J tumors from the perspective of DNA methylation and promoter mutation. Methylation sequencing of the chTERT amplicon showed that ALV-J replication promoted the methylation level of the chTERT promoter. And the methylation level of the chTERT promoter in ALV-J tumors was significantly higher than that in tumor-adjacent and normal tissues. Compared with the tumor-adjacent and normal tissues, the chTERT promoter in each ALV-J tumors tested had a mutation of −183 bp C > T, and 36.0% (9/25) of the tumors also had mutations of −184 bp T > C, −73 bp::GGCCC and −56 bp A > T in the chTERT promoter, which formed the binding sites for the transcription factors NFAT5, TFAP2A and ZEB1, respectively. The results of RT–qPCR and Western blotting showed that the occurrence of these mutations significantly increased the expression level of chTERT. In conclusion, this study demonstrated that the high expression of chTERT in ALV-J tumors is positively correlated with the level of hypermethylation and mutation in its promoter, which provides a new perspective for further research on the molecular mechanism of chTERT in ALV-J tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

The expression level of chicken telomerase reverse transcriptase in tumors induced by ALV-J is positively correlated with methylation and mutation of its promoter region

Xiang

Chen

et al. 2022

Vet Res

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“…Methylation-specific polymerase chain reaction and Sanger sequencing of the Cytosine-Guanine dinucleotide (CpG) sites 74–98 within the O6-methylguanine-DNA-methlytransferase (MGMT) promotor region were used to analyze MGMT promotor status, as previously described [ 12 ]. Isocitrate dehydrogenase 1/2 was assessed per pyrosequencing; telomerase reverse transcriptase promotor mutation (TERT) status was analyzed using Sanger sequencing [ 13 , 14 ].…”

Section: Methodsmentioning

confidence: 99%

Frequency and Prognostic Relevance of Volumetric MRI Changes in Contrast- and Non-Contrast-Enhancing Tumor Compartments between Surgery and Radiotherapy of IDHwt Glioblastoma

Teske

Niyazi

et al. 2023

Cancers

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In newly diagnosed IDH-wildtype glioblastoma, the frequency and prognostic relevance of tumor regrowth between resection and the initiation of adjuvant radiochemotherapy are unclear. In this retrospective single-center study we included 64 consecutive cases, for whom magnetic resonance imaging (MRI) was available for both the volumetric assessment of the extent of resection immediately after surgery as well as the volumetric target delineation before the initiation of adjuvant radiochemotherapy (time interval: 15.5 ± 1.9 days). Overall, a median new contrast-enhancement volume was seen in 21/64 individuals (33%, 1.5 ± 1.5 cm3), and new non-contrast lesion volume in 18/64 patients (28%, 5.0 ± 2.3 cm3). A multidisciplinary in-depth review revealed that new contrast-enhancement was either due to (I) the progression of contrast-enhancing tumor remnants in 6/21 patients or (II) distant contrast-enhancing foci or breakdown of the blood–brain barrier in previously non-contrast-enhancing tumor remnants in 5/21 patients, whereas it was unspecific or due to ischemia in 10/21 patients. For non-contrast-enhancing lesions, three of eighteen had progression of non-contrast-enhancing tumor remnants and fifteen of eighteen had unspecific changes or changes due to ischemia. There was no significant association between findings consistent with tumor regrowth and a less favorable outcome (overall survival: 14 vs. 19 months; p = 0.423). These findings support the rationale that analysis of the postsurgical remaining tumor-volume for prognostic stratification should be carried out on immediate postoperative MRI (<72 h), as unspecific changes are common. However, tumor regrowth including distant foci may occur in a subset of IDH-wildtype glioblastoma patients diagnosed per WHO 2021 classification. Thus, MRI imaging prior to radiotherapy should be obtained to adjust radiotherapy planning accordingly.

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“…O6-Methylguanine-DNA-methlytransferase (MGMT) promotor, telomerase reverse transcriptase promotor mutation, isocitrate dehydrogenase 1/2 and BRAF mutation status, as well as loss of heterozygosity of 1p/19q were analyzed as previously described [ 3 , 28 ]. For extended molecular diagnostics, next-generation sequencing and DNA methylation-based tumor diagnostics were performed whenever deemed clinically necessary [ 4 ].…”

Section: Methodsmentioning

confidence: 99%

Shunt dependency in supratentorial intraventricular tumors depends on the extent of tumor resection

et al. 2023

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Background Supratentorial intraventricular tumors (SIVTs) are rare lesions of various entities characteristically presenting with hydrocephalus and often posing a surgical challenge due to their deep-seated localization. We aimed to elaborate on shunt dependency after tumor resection, clinical characteristics, and perioperative morbidity. Methods We retrospectively searched the institutional database for patients with supratentorial intraventricular tumors treated at the Department of Neurosurgery of the Ludwig-Maximilians-University in Munich, Germany, between 2014 and 2022. Results We identified 59 patients with over 20 different SIVT entities, most often subependymoma (8/59 patients, 14%). Mean age at diagnosis was 41 ± 3 years. Hydrocephalus and visual symptoms were observed in 37/59 (63%) and 10/59 (17%) patients, respectively. Microsurgical tumor resection was provided in 46/59 patients (78%) with complete resection in 33/46 patients (72%). Persistent postoperative neurological deficits were encountered in 3/46 patients (7%) and generally mild in nature. Complete tumor resection was associated with less permanent shunting in comparison to incomplete tumor resection, irrespective of tumor histology (6% versus 31%, p = 0.025). Stereotactic biopsy was utilized in 13/59 patients (22%), including 5 patients who received synchronous internal shunt implantation for symptomatic hydrocephalus. Median overall survival was not reached and did not differ between patients with or without open resection. Conclusions SIVT patients display a high risk of developing hydrocephalus and visual symptoms. Complete resection of SIVTs can often be achieved, preventing the need for long-term shunting. Stereotactic biopsy along with internal shunting represents an effective approach to establish diagnosis and ameliorate symptoms if resection cannot be safely performed. Due to the rather benign histology, the outcome appears excellent when adjuvant therapy is provided.

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Extent, pattern, and prognostic value of MGMT promotor methylation: does it differ between glioblastoma and IDH-wildtype/TERT-mutated astrocytoma?

Cited by 7 publications

References 28 publications

The expression level of chicken telomerase reverse transcriptase in tumors induced by ALV-J is positively correlated with methylation and mutation of its promoter region

The expression level of chicken telomerase reverse transcriptase in tumors induced by ALV-J is positively correlated with methylation and mutation of its promoter region

Frequency and Prognostic Relevance of Volumetric MRI Changes in Contrast- and Non-Contrast-Enhancing Tumor Compartments between Surgery and Radiotherapy of IDHwt Glioblastoma

Shunt dependency in supratentorial intraventricular tumors depends on the extent of tumor resection

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