Development of a Rapid and Sensitive IDH1/2 Mutation Detection Method for Glial Tumors and a Comparative Mutation Analysis of 236 Glial Tumor Samples

Avşar, Timuçin; Sursal, Alihan; Turan, Gizem; Yigit, Berfu Nur; Altunsu, Deniz; Cantasir, Kutay; Duyu, Gözde; Bayoumi, Ahmed B.; Yapıcıer, Özlem; Acar, Melih; Kılıç, Türker

doi:10.1007/s40291-020-00461-y

Cited by 8 publications

(5 citation statements)

References 25 publications

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“…The maximum MEG3 expression was observed in Grade 3 tumours indicating the contribution of IDH1 mutations since IDH1 mutant gliomas are the most frequently observed among all the grades of glioma tumours. 28 Finally, MEG3 suppression was found to possibly induce apoptotic cell death. Previous studies showed that MEG3 overexpression would induce apoptosis in lung carcinoma and glioma cells.…”

Section: Discussionmentioning

confidence: 98%

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Silencing of the MEG3 gene promoted anti‐cancer activity and drug sensitivity in glioma

Degirmenci,

Unver,

Kilic

et al. 2023

J Cellular Molecular Medi

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Aberrant expression of MEG3 has been shown in various cancers. The purpose of this study is to evaluate the effect of MEG3 on glioma cells and the use of potential chemotherapeutics in glioma by modulating MEG3 expression. Cell viability, migration and chemosensitivity were assayed. Cell death was evaluated in MEG3 overexpressing and MEG3 suppressed cells. MEG3 expression was compared in patient‐derived glioma cells concerning IDH1 mutation and WHO grades. Silencing of MEG3 inhibited cell proliferation and reduced cell migration while overexpression of MEG3 promoted proliferation in glioma cells. MEG3 inhibition improved the chemosensitivity of glioma cells to 5‐fluorouracil (5FU) but not to navitoclax. On the other hand, there is no significant effect of MEG3 expression on temozolamide (TMZ) treatment which is a standard chemotherapeutic agent in glioma. Suppression of the MEG3 gene in patient‐derived oligodendroglioma cells also showed the same effect whereas glioblastoma cell proliferation and chemosensitivity were not affected by MEG3 inhibition. Further, as a possible cell death mechanism of action apoptosis was investigated. Although MEG3 is a widely known tumour suppressor gene and its loss is associated with several cancer types, here we reported that MEG3 inhibition can be used for improving the efficiency of known chemotherapeutic drug sensitivity. We propose that the level of MEG3 should be evaluated in the treatment of different glioma subtypes that are resistant to effective drugs to increase the potential effective drug applications.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Silencing of the MEG3 gene promoted anti‐cancer activity and drug sensitivity in glioma

Degirmenci,

Unver,

Kilic

et al. 2023

J Cellular Molecular Medi

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“…14 In the past decade, researchers have tried detecting gene mutations quickly through different detection technologies (Table 3). 10,[14][15][16][17][18][19][20][21][22][23] There are 2 main technologies: mass spectrum (MS) and PCR. Between these methods, MS has the advantage of fast detection, but because its detection principle is based on the metabolite 2hydroxyglutaric acid (2-HG) as an indirect reflection of the mutation status of IDH, the application of MS has certain limitations, namely, it cannot be used for IDH typing or for detecting other molecular mutations.…”

Section: Discussionmentioning

confidence: 99%

Application of Intraoperative Rapid Molecular Diagnosis in Precision Surgery for Glioma: Mimic the World Health Organization CNS5 Integrated Diagnosis

Xue

Han

et al. 2022

Neurosurgery

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BACKGROUND:With the advent of the molecular era, the diagnosis and treatment systems of glioma have also changed. A single histological type cannot be used for prognosis grade. Only by combining molecular diagnosis can precision medicine be realized.OBJECTIVE:To develop an automatic integrated gene detection system (AIGS) for intraoperative detection in glioma and to explore its positive role in intraoperative diagnosis and treatment.METHODS:We analyzed the isocitrate dehydrogenase 1 (IDH1) mutation status of 105 glioma samples and evaluated the product's potential value for diagnosis; 37 glioma samples were detected intraoperatively to evaluate the feasibility of using the product in an actual situation. A blinding method was used to evaluate the effect of the detection technology on the accuracy of intraoperative histopathological diagnosis by pathologists. We also reviewed the current research status in the field of intraoperative molecular diagnosis.RESULTS:Compared with next-generation sequencing, the accuracy of AIGS in detecting IDH1 was 100% for 105 samples and 37 intraoperative samples. The blind diagnostic results were compared between the 2 groups, and the molecular information provided by AIGS increased the intraoperative diagnostic accuracy of glioma by 16.2%. Using the technical advantages of multipoint synchronous detection, we determined the tumor molecular margins for 5 IDH-positive patients and achieved accurate resection at the molecular level.CONCLUSION:AIGS can quickly and accurately provide molecular information during surgery. This methodology not only improves the accuracy of intraoperative pathological diagnosis but also provides an important molecular basis for determining tumor margins to facilitate precision surgery.

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“…The maximum MEG3 expression was observed in Grade III tumors indicating the contribution of IDH1 mutations since IDH1 mutant gliomas are the most frequently observed amongst all the grades of glioma tumors. (Avsar et al 2020) Finally, MEG3 suppression was found to induce apoptotic cell death. Previous studies showed that MEG3 overexpression would induce apoptosis in lung carcinoma and glioma cells.…”

Section: )mentioning

confidence: 98%

Silencing of MEG3 gene promoted anti-cancer activity and drug sensitivity in glioma

Avşar

Degirmenci

Kilic

2022

Preprint

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Aberrant expression of MEG3 has been shown in various cancers. The purpose of this study is to evaluate the effect of MEG3 on glioma cells including U87MG and patient-derived primary tumors cells and compare with nonglial HUVEC cells. Cell viability, migration and chemo sensitivity was assayed. Apoptosis was evaluated in MEG3 overexpressing and MEG3 suppressed cells. MEG3 expression was compared in patient-derived tumor cells with respect to IDH1 mutation status and WHO-grades. Silencing of MEG3 inhibited cell proliferation and reduced cell migration while overexpression of MEG3 promoted cell proliferation in glioma cells. MEG3 inhibition improved chemo sensitivity of glioma cells to 5-fluorouracil(5FU) but not to navitoclax. Suppression of MEG3 gene in patient-derived oligodendroglioma cells also showed the same effect whereas glioblastoma cell proliferation and chemo sensitivity were not affected by MEG3 inhibition. Further, cell death mechanism of action was found as apoptosis. Although MEG3 is a widely known tumor suppressor gene and its loss is associated with several cancer types, here we reported that MEG3 inhibition can be used in drug sensitivity for improving efficiency of known chemotherapeutics. We propose that the level of MEG3 should be evaluated in treatment of different glioma subtypes that are resistant to effective drugs.

show abstract

Development of a Rapid and Sensitive IDH1/2 Mutation Detection Method for Glial Tumors and a Comparative Mutation Analysis of 236 Glial Tumor Samples

Cited by 8 publications

References 25 publications

Silencing of the MEG3 gene promoted anti‐cancer activity and drug sensitivity in glioma

Silencing of the MEG3 gene promoted anti‐cancer activity and drug sensitivity in glioma

Application of Intraoperative Rapid Molecular Diagnosis in Precision Surgery for Glioma: Mimic the World Health Organization CNS5 Integrated Diagnosis

Silencing of MEG3 gene promoted anti-cancer activity and drug sensitivity in glioma

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