scholarly journals Genome‐wide methylomic analyses identify prognostic epigenetic signature in lower grade glioma

2021 ◽  
Author(s):  
Wenna Guo ◽  
Shanshan Ma ◽  
Yanting Zhang ◽  
Hongtao Liu ◽  
Ya Li ◽  
...  
Keyword(s):  
Lower Grade ◽  
Genome Wide ◽  
Lower Grade Glioma

scholarly journals Big data visualization identifies the multidimensional molecular landscape of human gliomas

2016 ◽  
Vol 113 (19) ◽  
pp. 5394-5399 ◽  
Author(s):  
Hamid Bolouri ◽  
Lue Ping Zhao ◽  
Eric C. Holland
Keyword(s):  
Drug Targets ◽  
The Cancer Genome Atlas ◽  
Lower Grade ◽  
Single Nucleotide ◽  
Big Data Visualization ◽  
Genome Wide ◽  
Lower Grade Glioma ◽  
Distinct Sequence ◽  
Cancer Genome Atlas ◽  
Molecular Landscape

We show that visualizing large molecular and clinical datasets enables discovery of molecularly defined categories of highly similar patients. We generated a series of linked 2D sample similarity plots using genome-wide single nucleotide alterations (SNAs), copy number alterations (CNAs), DNA methylation, and RNA expression data. Applying this approach to the combined glioblastoma (GBM) and lower grade glioma (LGG) The Cancer Genome Atlas datasets, we find that combined CNA/SNA data divide gliomas into three highly distinct molecular groups. The mutations commonly used in clinical evaluation of these tumors are regionally distributed in these plots. One of the three groups is a mixture of GBM and LGG that shows similar methylation and survival characteristics to GBM. Altogether, our approach identifies eight molecularly defined glioma groups with distinct sequence/expression/methylation profiles. Importantly, we show that regionally clustered samples are enriched for specific drug targets.

scholarly journals GENE-13. GENOMIC AND RADIOMIC LANDSCAPE OF IDH WILDTYPE-TERT PROMOTER MUTATION IN LOWER-GRADE GLIOMAS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi100-vi100
Author(s):  
Shuai Liu ◽  
Chuanbao Zhang ◽  
Xiaoguang Qiu
Keyword(s):  
World Health ◽  
Genetic Lineage ◽  
Lower Grade ◽  
Imaging Data ◽  
Who Grade ◽  
Non Invasive ◽  
Tert Promoter ◽  
Genome Wide ◽  
Lower Grade Glioma ◽  
Health Organization

Abstract BACKGROUND Recently, a rare subset of lower grade glioma (LoG), characterized by wild-type isocitrate dehydrogenase (IDH) and mutated TERT promoter (IDHWT-TERTpMut), has been highlighted for its dismal clinical behavior and classified as world health organization (WHO) grade IV. METHODS We examined this distinct tumor subset through genome-wide analysis of 745 gliomas and radiomic analysis of 129 LoGs. RESULTS We found that the prognosis and genetic lineage of IDHWT-TERTpMut LoGs were similar to those of glioblastoma. Importantly, a signature of 7 radiomic features from magnetic resonance imaging data differentiated IDHWT-TERTpMut LoGs from other LoGs. In addition, we found the radiomic related genes involved in many tumorigenic processes. CONCLUSIONS Overall, our findings suggest that the biological characteristics of IDHWT-TERTpMut LoGs and the radiomic signature could help in the non-invasive diagnosis of this tumor subtype.

scholarly journals RUNX1 and REXO2 are associated with the heterogeneity and prognosis of IDH wild type lower grade glioma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Ji Zhang ◽  
Hua Cao
Keyword(s):  
Transcription Factor ◽  
Low Frequency ◽  
Tumor Grade ◽  
The Cancer Genome Atlas ◽  
Lower Grade ◽  
Wild Type ◽  
Lower Grade Glioma ◽  
Cancer Genome Atlas ◽  
Worse Prognosis ◽  
Genome Atlas

AbstractBased on isocitrate dehydrogenase (IDH) alterations, lower grade glioma (LGG) is divided into IDH mutant and wild type subgroups. However, the further classification of IDH wild type LGG was unclear. Here, IDH wild type LGG patients in The Cancer Genome Atlas and Chinese Glioma Genome Atlas were divided into two sub-clusters using non-negative matrix factorization. IDH wild type LGG patients in sub-cluster2 had prolonged overall survival and low frequency of CDKN2A alterations and low immune infiltrations. Differentially expressed genes in sub-cluster1 were positively correlated with RUNX1 transcription factor. Moreover, IDH wild type LGG patients with higher stromal score or immune score were positively correlated with RUNX1 transcription factor. RUNX1 and its target gene REXO2 were up-regulated in sub-cluster1 and associated with the worse prognosis of IDH wild type LGG. RUNX1 and REXO2 were associated with the higher immune infiltrations. Furthermore, RUNX1 and REXO2 were correlated with the worse prognosis of LGG or glioma. IDH wild type LGG in sub-cluster2 was hyper-methylated. REXO2 hyper-methylation was associated with the favorable prognosis of LGG or glioma. At last, we showed that, age, tumor grade and REXO2 expression were independent prognostic factors in IDH wild type LGG.

scholarly journals QOLP-37. QUALITATIVE RESEARCH IN LOWER GRADE GLIOMA: UNDERSTANDING SIGNS, SYMPTOMS, AND DISEASE IMPACTS DURING EXPECTANT MANAGEMENT

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi206-vi206
Author(s):  
Audra Boscoe ◽  
Ted Wells ◽  
Christina Graham ◽  
Caitlin Pohl ◽  
Brooke Witherspoon ◽  
...  
Keyword(s):  
Treatment Options ◽  
Expectant Management ◽  
Signs And Symptoms ◽  
Molecular Therapy ◽  
Patient Specific ◽  
Lower Grade ◽  
Concept Elicitation ◽  
Post Surgery ◽  
Lower Grade Glioma ◽  
Isocitrate Dehydrogenase Mutation

Abstract BACKGROUND Patients with lower grade glioma (LGG) (i.e., grade II or III) have limited treatment options. After surgical resection of their tumor, patients will undergo either a period of expectant management (watch and wait) or treatment with adjuvant chemotherapy and/or radiotherapy. Approximately 80% of patients with LGG have an isocitrate dehydrogenase mutation, which is a viable target for molecular therapy. This offers a therapeutic intervention that could potentially delay the need for chemotherapy and/or radiotherapy in select patients. Several prognostic and patient-specific factors contribute to the decision to recommend expectant management, including concerns about the side effects of chemotherapy and radiotherapy. The aim of this project was to understand patients’ signs and symptoms during the expectant management period and how LGG impacts their lives. METHODS Concept elicitation interviews were conducted in the US with patients with LGG as well as key opinion leaders (KOLs) with experience treating patients with LGG. Interview data were analyzed using Atlas.ti, and patient data were reviewed against KOL data. RESULTS Seven patients with ≥ 3 months of expectant management experience and three KOLs were interviewed. During their expectant management periods, patients reported 12 signs/symptoms, mostly related to deficits in cognition. Patients reported 16 impacts across four categories, with a substantial proportion of the impacts identified as negatively affecting emotional function. The signs/symptoms and impacts reported by patients were generally also reported by KOLs. During expectant management, patients typically resume their original quality of life post-surgery, but may also experience anxiety. Patients and KOLs indicated a preference for expectant management and delaying chemotherapy or radiotherapy. CONCLUSIONS Patient and KOL interviews characterized the LGG experience and indicated a preference for expectant management, which may be supported by therapies that delay the initiation of chemotherapy and/or radiotherapy.

The Role of Surgery in IDH-Wild-Type Lower-Grade Gliomas: Threshold at a High Extent of Resection Should be Pursued

Neurosurgery ◽  
2021 ◽  
Author(s):  
Peng Wang ◽  
Chen Luo ◽  
Peng-jie Hong ◽  
Wen-ting Rui ◽  
Shuai Wu
Keyword(s):  
Cox Regression ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Lower Grade ◽  
Wild Type ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Lower Grade Glioma ◽  
Clinical Benefits

Abstract BACKGROUND While maximizing extent of resection (EOR) is associated with longer survival in lower-grade glioma (LGG) patients, the number of cases remains insufficient in determining a EOR threshold to elucidate the clinical benefits, especially in IDH-wild-type LGG patients. OBJECTIVE To identify the effects of EOR on the survival outcomes of IDH-wild-type LGG patients. METHODS IDH-wild-type LGG patients were retrospectively reviewed. The effect of EOR and other predictor variables on overall survival (OS) and progression-free survival (PFS) was analyzed using Cox regression models and the Kaplan-Meier method. RESULTS A total of 94 patients (median OS: 48.9 mo; median follow-up: 30.6 mo) were included in this study. In the multivariable Cox regression analysis, postoperative residual volume was associated with prolonged OS (HR = 2.238; 95% confidence interval [CI], 1.130-4.435; P = .021) and PFS (HR = 2.075; 95% CI, 1.113-3.869; P = .022). Thresholds at a minimum EOR of 97.0% or a maximum residue of 3.0 cm3 were necessary to impact OS positively. For the telomerase reverse transcriptase (TERT)p-wild-type group, such an association was absent. Significant differences in survival existed between the TERTp-wild-type and mutant patients who underwent relatively incomplete resections (residual ≥2.0 cm3 + TERTp wild type: median OS of 62.6 mo [95% CI: 39.7-85.5 mo]; residual ≥2.0 cm3 + TERTp mutant: median OS of 20.0 mo [95% CI:14.6-25.4 mo]). CONCLUSION Our results support the core role of maximal safe resection in the treatment of IDH-wild-type LGGs, especially for IDH-wild-type + TERTp-mutant LGGs. Importantly, the survival benefits of surgery could only be elucidated at a high EOR cut-off point.

Back to the Future: Charting the Direction of Lower Grade Glioma Trials With Lessons From the Present and Past

2022 ◽  
Vol 112 (1) ◽  
pp. 30-34
Author(s):  
Michelle M. Kim ◽  
Jona A. Hattangadi-Gluth ◽  
Kristin J. Redmond ◽  
Daniel M. Trifiletti ◽  
Scott G. Soltys ◽  
...  
Keyword(s):  
Lower Grade ◽  
Lower Grade Glioma ◽  
The Future
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