Association between IDH1/2 mutations and brain glioma grade

Deng, Lisheng; Xiong, Pengju; Luo, Yun-Hui; Bu, Xiao; Qian, Suokai; Zhong, Wuzhao; Lv, Shunqing

doi:10.3892/ol.2018.9317

Cited by 35 publications

(47 citation statements)

References 29 publications

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“…Subsequently we sought to assess the frequency of IDH1/2 mutation, 1p/19q co-deletion status and other pathological features with respect to proliferation rate of cultured gliomas. In accordance with several previous reports (29,30), IDH1/2 mutations were essentially found among grade II with negligible association to proliferation rate. Similarly MIB1 expression were found exclusively in the high-grade, but not in low-grade, irrespective of proliferation status of glioma cultures.…”

Section: Discussionsupporting

confidence: 93%

Patients’ Derived Short-Term Glioma Culture: Identification of Aggressive, Drug-Resistant Phenotype

Beevi¹,

Verma²,

Panigrahi

et al. 2020

Preprint

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Background: Low-grade gliomas are mostly played down as less fatal malignancy despite the fact that most of them eventually progress to high grade thereby leading to death. In vitro glioma cultures have been emerged as a standard model to get insight into phenotypic transformation, drug response and tumor relapse. In this study, attempt was made to establish comprehensive patient-specific short-term cultures comprising of both low-grade and high-grade malignant glioma.Methods: 50 patients with MRI diagnosed malignant glioma were recruited for this study. Fresh surgical tumor tissues were used for the establishment of primary culture. Patients' samples were analyzed for the presence of IDH1/2 mutations, 1p/19q co-deletion, MIB1 and p53. Established primary glioma culture were evaluated for proliferation rate, sensitivity to temozolomide and expression pattern of Glial-Mesenchymal Transition (GMT) markers. Results: Short-term glioma cultures were successfully established in 40 clinical samples. Glioma cultures, irrespective of tumor grades, displayed two distinct pattern of growth kinetics -one with shorter doubling time (high-proliferating) and another group with longer doubling time (lowproliferating). Significant distinctive features were noticed between these two groups in terms of response to temozolomide, expression pattern of GMT markers and their association with clinical/pathological features of malignant glioma. Conclusion: Our findings effectively demonstrated the practicality of development of short-term glioma culture model toward a functional approach for personalized medicine. Our model further revealed the presence of highly proliferative, drug-resistant phenotype among low-grade gliomas. Hence, short-term culture model could be an important prognostic tool to predict patient clinical responses and also provide cue about imminent tumour relapse.

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Section: Discussionsupporting

confidence: 93%

Patients’ Derived Short-Term Glioma Culture: Identification of Aggressive, Drug-Resistant Phenotype

Beevi¹,

Verma²,

Panigrahi

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…No patients with ependymoma showed this mutation. Previous studies have indeed shown the association of IDH1 mutation with histology and grading of gliomas (Yan et al, 2009;Qi et al, 2014;Yusoff et al, 2016;Wang et al, 2016;Deng et al, 2018). The percentage of oligodendroglioma samples with IDH1 mutation in our study is quite similar to those in previous studies (Mukasa et al, 2012;Senhaji et al, 2016;Wang et al, 2016).…”

Section: Discussionsupporting

confidence: 91%

Clinicopathological Features and Prognosis of Indonesian Patients with Gliomas with IDH Mutation: Insights into Its Significance in a Southeast Asian Population

Malueka

Dwianingsih

Bayuangga

et al. 2020

Asian Pac J Cancer Prev

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Background: Gliomas remain one of the most common primary brain tumors. Mutations in the isocitrate dehydrogenase (IDH) gene are associated with a distinct set of clinicopathological profiles. However, the distribution and significance of these mutations have never been studied in the Indonesian population. This study aimed to elucidate the association between IDH mutations and clinicopathological as well as prognostic profiles of Indonesian patients with gliomas. Methods: In total, 106 patients with gliomas were recruited from a tertiary academic medical center in Yogyakarta, Indonesia. Formalin-fixed paraffin-embedded and fresh tissue specimens were obtained and sectioned for hematoxylin-eosin staining and immunohistochemical examinations. Genomic DNA was isolated and analyzed for the presence of IDH mutations using standard polymerase chain reaction and nucleotide sequencing methods. Clinicopathological data were collected from medical records. Results: Although no IDH2 mutation was identified, IDH1 mutations were found in 23 (21.7%) of the patients. Patients with IDH1 mutations tended to have a history of smoking and a shorter interval between onset of symptoms and initial surgical interventions. Frontal lobe involvement, oligodendroglial histology, lower Ki67 expression, WHO grades II and III gliomas, and methylated O6-methylguanine-DNA methyltransferase (MGMT) promoters were significantly associated with the presence of IDH1 mutations. Compared with patients with IDH1-wild-type, patients with IDH1 mutation were observed to have a longer overall survival. Conclusions: IDH1 mutations are associated with certain clinicopathological and prognostic profiles in Indonesian patients with gliomas. This finding demonstrates the importance of identifying IDH mutations as part of the management of patients with glioma in Indonesia.

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“…Therefore, we propose a novel radiomics set by using F-score feature selection. Moreover, because IDH1 mutation is related to drug response of GBM [14,15], here, we compare the MGMT status in IDH1 wildtype mutation by using a highly efficient radiomics feature set and advanced machine learning techniques.…”

Section: Introductionmentioning

confidence: 99%

XGBoost Improves Classification of MGMT Promoter Methylation Status in IDH1 Wildtype Glioblastoma

Thi

Chiu

et al. 2020

JPM

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Approximately 96% of patients with glioblastomas (GBM) have IDH1 wildtype GBMs, characterized by extremely poor prognosis, partly due to resistance to standard temozolomide treatment. O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation status is a crucial prognostic biomarker for alkylating chemotherapy resistance in patients with GBM. However, MGMT methylation status identification methods, where the tumor tissue is often undersampled, are time consuming and expensive. Currently, presurgical noninvasive imaging methods are used to identify biomarkers to predict MGMT methylation status. We evaluated a novel radiomics-based eXtreme Gradient Boosting (XGBoost) model to identify MGMT promoter methylation status in patients with IDH1 wildtype GBM. This retrospective study enrolled 53 patients with pathologically proven GBM and tested MGMT methylation and IDH1 status. Radiomics features were extracted from multimodality MRI and tested by F-score analysis to identify important features to improve our model. We identified nine radiomics features that reached an area under the curve of 0.896, which outperformed other classifiers reported previously. These features could be important biomarkers for identifying MGMT methylation status in IDH1 wildtype GBM. The combination of radiomics feature extraction and F-core feature selection significantly improved the performance of the XGBoost model, which may have implications for patient stratification and therapeutic strategy in GBM.

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Association between IDH1/2 mutations and brain glioma grade

Cited by 35 publications

References 29 publications

Patients’ Derived Short-Term Glioma Culture: Identification of Aggressive, Drug-Resistant Phenotype

Patients’ Derived Short-Term Glioma Culture: Identification of Aggressive, Drug-Resistant Phenotype

Clinicopathological Features and Prognosis of Indonesian Patients with Gliomas with IDH Mutation: Insights into Its Significance in a Southeast Asian Population

XGBoost Improves Classification of MGMT Promoter Methylation Status in IDH1 Wildtype Glioblastoma

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