Predicting TERT promoter mutation using MR images in patients with wild-type IDH1 glioblastoma

Yamashita, Koji; Hatae, Ryusuke; Hiwatashi, Akio; Togao, Osamu; Kikuchi, Kazufumi; Momosaka, Daichi; Yamashita, Yasuo; Kuga, Daisuke; Hata, Nobuhiro; Yoshimoto, Koji; Suzuki, Satoshi; Iwaki, Toru; Iihara, Koji; Honda, Hiroshi

doi:10.1016/j.diii.2019.02.010

Cited by 29 publications

(33 citation statements)

References 28 publications

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“…However, another report from Japan indicated that 58%‐59% of GBM had mutations in TERTp , 38,39 suggesting that TERTp mutations may be less frequent in Japan than in other countries. Previous reports have shown that patients with the TERTp ‐wildtype GBM were significantly younger, on average, than those with TERTp ‐mutant GBM, 34,36,40,41 contrasting with our results. However, when we analyzed 301 cases conclusively diagnosed with IDH ‐wildtype GBM, part of a previously published Japanese large cohort, 39 the average age of patients with TERTp ‐wildtype and TERTp ‐mutant GBMs was statistically comparable (61.02 vs 63.36 y, P = .065), in line with our findings.…”

Section: Discussioncontrasting

confidence: 99%

“…Interestingly, in our cohorts, there was no difference in the average age of patients with TERTp ‐wildtype GBM or TERTp ‐mutant GBM. However, when we excluded Group C, patients with TERTp ‐wildtype GBM were significantly younger than those with TERTp ‐mutant GBM, in accordance with previous studies 34,36,40,41 . No distinct difference in survival was observed for patients with TERTp ‐wildtype GBM or TERTp ‐mutant GBM in our cohorts.…”

Section: Discussionsupporting

confidence: 90%

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A tailored next‐generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas

et al. 2020

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 90%

A tailored next‐generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas

et al. 2020

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“…Yamashita et al [31] investigated 112 GBM patients with IDH wild type based on radiomics and revealed that TERT promoter mutations were correlated with the percentage of necrotic volume and age. Our further research demonstrated that CNV dramatically upregulated in TERTm than TERTw,…”

Section: Discussionmentioning

confidence: 99%

Noninvasive Prediction of TERT Promoter Mutations in High-Grade Glioma by Radiomics Analysis Based on Multiparameter MRI

Tian

et al. 2020

BioMed Research International

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Objectives. To investigate the predictors of telomerase reverse transcriptase (TERT) promoter mutations in adults suffered from high-grade glioma (HGG) through radiomics analysis, develop a noninvasive approach to evaluate TERT promoter mutations. Methods. 126 adult patients with HGG (88 in the training cohort and 38 in the validation cohort) were retrospectively enrolled. Totally 5064 radiomics features were, respectively, extracted from three VOIs (necrosis, enhanced, and edema) in MRI. Firstly, an optimal radiomics signature (Radscore) was established based on LASSO regression. Secondly, univariate and multivariate logistic regression analyses were performed to investigate important potential variables as predictors of TERT promoter mutations. Besides, multiparameter models were established and evaluated. Eventually, an optimal model was visualized as radiomics nomogram for clinical evaluations. Results. 6 radiomics features were selected to build Radscore signature through LASSO regression. Among them, 5 were from necrotic VOIs and 1 was from enhanced ones. With univariate and multivariate analysis, necrotic volume percentages of core (CNV), Age, Cho/Cr, Lac, and Radscore were significantly higher in TERTm than in TERTw (p<0.05). 4 models were built in our study. Compared with Model B (Age, Cho/Cr, Lac, and Radscore), Model A (Age, Cho/Cr, Lac, Radscore, and CNV) has a larger AUC in both training (0.955 vs. 0.917, p=0.049) and validation (0.889 vs. 0.868, p=0.039) cohorts. It also has higher performances in net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) evaluation. Conclusively, Model A was visualized as a radiomics nomogram. Calibration curve shows a good agreement between estimated and actual probabilities. Conclusions. Age, Cho/Cr, Lac, CNV, and Radscore are important indicators for TERT promoter mutation predictions in HGG. Tumor necrosis seems to be closely related to TERT promoter mutations. Radiomics nomogram based on multiparameter MRI and CNV has higher prediction accuracies.

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“… 3–5 Other reports from Japan also showed relatively low frequencies of TERT p mutations among IDH wild-type GBM, ranging from 50% to 70%. 6 , 9 , 29 Thus, racial differences in the frequency of TERT p mutations may exist. One possible explanation for the low frequency of TERT p mutations in the Japanese cohort is that other mechanisms involved with replicative immortality in TERT p wild-type GBM.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding imaging analysis, necrosis detected through magnetic resonance imaging (MRI) has been reported to indicate the presence of TERT p mutation. 9 However, predicting the TERT p status by preoperative imaging study alone remains difficult.…”

mentioning

confidence: 99%

TERT promoter mutation associated with multifocal phenotype and poor prognosis in patients with IDH wild-type glioblastoma

Kikuchi

Shibahara

Yamaki

et al. 2020

Neuro-Oncology Advances

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Background Although mutations in the promoter region of the telomerase reverse transcriptase gene (TERTp) are the most common alterations in glioblastoma (GBM), their clinical significance remains unclear. Therefore, we investigated the impact of TERTp status on patient outcome and clinicopathological features in patients with GBM over a long period of follow-up Methods We retrospectively analyzed 153 cases of GBM. Six patients with isocitrate dehydrogenase 1 (IDH1) or H3F3A gene mutations were excluded from this study. Among the 147 cases of IDH wild-type GBM, 92 (62.6%) had the TERTp mutation. Clinical, immunohistochemical, and genetic factors (BRAF, TP53 gene mutation, CD133, ATRX expression, O 6-methylguanine-DNA methyltransferase [MGMT] promoter methylation) and copy number alterations (CNAs) were investigated Results GBM patients with the TERTp mutation were older at first diagnosis versus those with TERTp wild type (66.0 vs. 60.0 years, respectively, P=0.034), and had shorter progression-free survival (7 vs. 10 months, respectively, P=0.015) and overall survival (16 vs. 24 months, respectively, P=0.017). Notably, magnetic resonance imaging performed showed that TERTp-mutant GBM was strongly associated with multifocal/distant lesions (P=0.004)According to the CNA analysis, TERTp mutations were positively correlated with EGFR amp/gain, CDKN2A deletion, and PTEN deletion; however, these mutations were negatively correlated with PDGFR amp/gain, CDK4 gain and TP53 deletion Conclusions TERTp mutations were strongly correlated with multifocal/distant lesions and poor prognosis in patients with IDH wild-type GBM. Less aggressive GBM with TERTp wild type may be a distinct clinical and molecular subtype of IDH wild type GBM.

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Predicting TERT promoter mutation using MR images in patients with wild-type IDH1 glioblastoma

Cited by 29 publications

References 28 publications

A tailored next‐generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas

A tailored next‐generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas

Noninvasive Prediction of TERT Promoter Mutations in High-Grade Glioma by Radiomics Analysis Based on Multiparameter MRI

TERT promoter mutation associated with multifocal phenotype and poor prognosis in patients with IDH wild-type glioblastoma

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