Classification based on mutations of<i>TERT</i>promoter and<i>IDH</i>characterizes subtypes in grade II/III gliomas

Yang, Pei; Cai, Jinquan; Yan, Wei; Zhang, Wei; Wang, Yinyan; Chen, Baoshi; Li, Guilin; Li, Shouwei; Wu, Chenxing; Yao, Kun; Li, Wenbin; Peng, Xiaoxia; You, Yongping; Chen, Ling; Jiang, Chuanlu; Qiu, Xiaoguang; Jiang, Tao

doi:10.1093/neuonc/now021

Cited by 98 publications

(81 citation statements)

References 48 publications

(56 reference statements)

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“…Alterations in TERT and ATRX are not only associated with certain histologic subgroups of gliomas, but also are associated with variable prognosis [3, 6, 12, 16, 21, 26, 28]. Our research team previously showed that molecular classification of gliomas based on IDH , TERT promoter mutations and 1p/19q codeletion status yields five subgroups that are independently associated with prognosis in grade II and III gliomas [6].…”

Section: Introductionmentioning

confidence: 99%

“…Our research team previously showed that molecular classification of gliomas based on IDH , TERT promoter mutations and 1p/19q codeletion status yields five subgroups that are independently associated with prognosis in grade II and III gliomas [6]. A similar classification of grade II and III infiltrating gliomas using only IDH and TERT promoter mutation status was also suggested [28]. Other groups demonstrated a role for ATRX in the classification of gliomas [12, 16].…”

Section: Introductionmentioning

confidence: 99%

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Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT

et al. 2017

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The “integrated diagnosis” for infiltrating gliomas in the 2016 revised World Health Organization (WHO) classification of tumors of the central nervous system requires assessment of the tumor for IDH mutations and 1p/19q codeletion. Since TERT promoter mutations and ATRX alterations have been shown to be associated with prognosis, we analyzed whether these tumor markers provide additional prognostic information within each of the five WHO 2016 categories. We used data for 1206 patients from the UCSF Adult Glioma Study, the Mayo Clinic and The Cancer Genome Atlas (TCGA) with infiltrative glioma, grades II–IV for whom tumor status for IDH, 1p/19q codeletion, ATRX, and TERT had been determined. All cases were assigned to one of 5 groups following the WHO 2016 diagnostic criteria based on their morphologic features, and IDH and 1p/19q codeletion status. These groups are: 1-Oligodendroglioma, IDH-mutant and 1p/19q-codeleted; 2- Astrocytoma, IDH-mutant; 3- Glioblastoma, IDH-mutant; 4- Glioblastoma, IDH-wildtype; and 5-Astrocytoma, IDH-wildtype. Within each group, we used univariate and multivariate Cox proportional hazards models to assess associations of overall survival with patient age at diagnosis, grade, and ATRX alteration status and/or TERT promoter mutation status. Among Group 1 IDH-mutant 1p/19q-codeleted oligodendrogliomas, the TERT-WT group had significantly worse overall survival than the TERT-MUT group (HR: 2.72, 95%CI: 1.05–7.04, p=0.04). In both Group 2, IDH-mutant astrocytomas and Group 3, IDH-mutant glioblastomas, neither TERT mutations nor ATRX alterations were significantly associated with survival. Among Group 4, IDH-wildtype glioblastomas, ATRX alterations were associated with favorable outcomes (HR: 0.36, 95% CI: 0.17–0.81, p=0.01). Among Group 5, IDH-wildtype astrocytomas, the TERT-WT group had significantly better overall survival than the TERT-MUT group (HR: 0.48, 95% CI: 0.27–0.87), p=0.02). Thus, we present evidence that in certain WHO 2016 diagnostic groups, testing for TERT promoter mutations or ATRX alterations may provide additional useful prognostic information.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT

et al. 2017

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“…No significant difference was observed between the CE and nCE groups with respect to age, sex, and O‐6‐methylguanine‐DNA methyltransferase (MGMT) promoter methylation status in both the training and validation sets ( P > 0.05). Mutations in IDH, a crucial prognostic biomarker for gliomas, were more common in the nCE group in both the training ( P = 0.038) and validation ( P = 0.043) sets. Additionally, there was no difference about 1p/19q status between the CE and nCE groups in the training set ( P > 0.05), while the frequency of 1p/19q co‐deletion was higher in the nCE group in the validation set ( P = 0.005).…”

Section: Resultsmentioning

confidence: 99%

Molecular profiles of tumor contrast enhancement: A radiogenomic analysis in anaplastic gliomas

Liu

Sun

et al. 2018

Cancer Medicine

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The presence of contrast enhancement (CE) on magnetic resonance (MR) imaging is conventionally regarded as an indicator for tumor malignancy. However, the biological behaviors and molecular mechanism of enhanced tumor are not well illustrated. The aim of this study was to investigate the molecular profiles associated with anaplastic gliomas (AGs) presenting CE on postcontrast T1‐weighted MR imaging. In this retrospective database study, RNA sequencing and MR imaging data of 91 AGs from the Cancer Genome Atlas (TCGA) and 64 from the Chinese Glioma Genome Atlas (CGGA) were collected. Gene set enrichment analysis (GSEA), significant analysis of microarray, generalized linear models, and Least absolute shrinkage and selection operator algorithm were used to explore radiogenomic and prognostic signatures of AG patients. GSEA indicated that angiogenesis and epithelial‐mesenchymal transition were significantly associated with post‐CE. Genes driving immune system response, cell proliferation, and focal adhesions were also significantly enriched. Gene ontology of 237 differential genes indicated consistent results. A 48‐gene signature for CE was identified in TCGA and validated in CGGA dataset (area under the curve = 0.9787). Furthermore, seven genes derived from the CE‐specific signature could stratify AG patients into two subgroups based on overall survival time according to corresponding risk score. Comprehensive analysis of post‐CE and genomic characteristics leads to a better understanding of radiology‐pathology correlations. Our gene signature helps interpret the occurrence of radiological traits and predict clinical outcomes. Additionally, we found nine prognostic quantitative radiomic features of CE and investigated the underlying biological processes of them.

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“…These mutations (mostly involving cytosolic IDH1 , lesser so mitochondrial IDH2 ) have important consequences for the epigenome and cause extensive DNA methylation in IDH-mutant diffuse gliomas (‘glioma-CpG island methylator phenotype’/G-CIMP) [22, 104]. In ‘canonical’ oligodendrogliomas, according to the recently published WHO classification of CNS tumors, an IDH1 or IDH2 mutation co-occurs with complete and combined deletion of chromosome arms 1p and 19q [20, 44, 56, 105, 164]. This complete 1p/19q codeletion not only constitutes the genetic hallmark of oligodendrogliomas, but also an important favorable prognostic and predictive marker.…”

Section: Introductionmentioning

confidence: 99%

Glioma: experimental models and reality

et al. 2017

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In theory, in vitro and in vivo models for human gliomas have great potential to not only enhance our understanding of glioma biology, but also to facilitate the development of novel treatment strategies for these tumors. For reliable prediction and validation of the effects of different therapeutic modalities, however, glioma models need to comply with specific and more strict demands than other models of cancer, and these demands are directly related to the combination of genetic aberrations and the specific brain micro-environment gliomas grow in. This review starts with a brief introduction on the pathological and molecular characteristics of gliomas, followed by an overview of the models that have been used in the last decades in glioma research. Next, we will discuss how these models may play a role in better understanding glioma development and especially in how they can aid in the design and optimization of novel therapies. The strengths and weaknesses of the different models will be discussed in light of genotypic, phenotypic and metabolic characteristics of human gliomas. The last part of this review provides some examples of how therapy experiments using glioma models can lead to deceptive results when such characteristics are not properly taken into account.

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Classification based on mutations ofTERTpromoter andIDHcharacterizes subtypes in grade II/III gliomas

Abstract: Our results showed that TERTp-mut combined with IDH-mut allowed simple classification of grade II/III gliomas for stratifying patients and clarifying diagnostic accuracy by supplementing standard histopathological criteria.

Cited by 98 publications

References 48 publications

Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT

Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT

Molecular profiles of tumor contrast enhancement: A radiogenomic analysis in anaplastic gliomas

Glioma: experimental models and reality

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