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

Higa, Nayuta; Akahane, Toshiaki; Yokoyama, Seiya; Yonezawa, Hajime; Uchida, Hiroyuki; Takajo, Tomoko; Kirishima, Mari; Hamada, Taiji; Matsuo, Keitaro; Shimizu, Fujio; Hanada, Tomoko; Hosoyama, Hiroshi; Yonenaga, Masanori; Sakamoto, Akihisa; Hiraki, Takao; Tanimoto, Akihide; Yoshimoto, Koji

doi:10.1111/cas.14597

Cited by 35 publications

(38 citation statements)

References 45 publications

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“…ddPCR techniques have a higher sensitivity than Sanger sequencing in the detection of IDH1 and TERTp mutations in glioma [ 29 , 30 , 31 ]. NGS assays also offer the possibility of deep detection and multiplexing the search for genomic alterations [ 32 , 33 , 34 , 35 , 36 ]. Euskirchen et al [ 37 ] described a pocket-size nanopore sequencing device that could provide same-day detection of structural variants, point mutations, and methylation profiling.…”

Section: Resultsmentioning

confidence: 99%

“…Among these fragments, circulating tumor DNA is the most described in the literature and can be used to detect TERTp mutations by ddPCR or NGS-based sequencing methods [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 43 ]. ddPCR allows for significant sequencing depth and is thus suitable for the detection of a small quantity of circulating tumor DNA as observed in the plasma of patients suffering from glioma.…”

Section: Resultsmentioning

confidence: 99%

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TERT Promoter Alterations in Glioblastoma: A Systematic Review

Olympios¹,

Gilard

Marguet

et al. 2021

Cancers

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Glioblastoma, the most frequent and aggressive primary malignant tumor, often presents with alterations in the telomerase reverse transcriptase promoter. Telomerase is responsible for the maintenance of telomere length to avoid cell death. Telomere lengthening is required for cancer cell survival and has led to the investigation of telomerase activity as a potential mechanism that enables cancer growth. The aim of this systematic review is to provide an overview of the available data concerning TERT alterations and glioblastoma in terms of incidence, physiopathological understanding, and potential therapeutic implications.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

TERT Promoter Alterations in Glioblastoma: A Systematic Review

Olympios¹,

Gilard

Marguet

et al. 2021

Cancers

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“…In this study, we collected higher number of samples than in our previous study [15]. We found that the frequency of EGFR mutations was low but the frequency of EGFR mutations in the kinase domain was high in wildtype-GBMs.…”

Section: Discussionmentioning

confidence: 84%

“…Next-generation sequencing NGS was performed using an amplicon-based glioma-tailored gene panel as described previously [15]. Amplicon sequences were aligned to the human reference genome GRCh37 (hg19) in the target region of the sequence.…”

Section: Dna Extraction and Quanti Cationmentioning

confidence: 99%

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Detection of EGFR Mutation Distribution and Transcriptional Variants in IDH-wildtype High-grade Gliomas using a Next-generation Sequencing Oncopanel

Higa¹,

Akahane²,

Hamada³

et al. 2021

Preprint

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Purpose: To detect the epidermal growth factor receptor gene (EGFR) mutation profile and transcriptional variants in high-grade gliomas (HGGs), we sequenced EGFR and evaluated the EGFR splicing profile using a next-generation sequencing (NGS) oncopanel. Methods: We analyzed 124 HGGs—10 grade Ⅲ IDH-wildtype anaplastic astrocytomas (AAs) and 114 grade Ⅳ IDH-wildtype glioblastomas (GBMs). Results: The EGFR mutations were observed in 6.0% of grade Ⅳ GBMs and in 33% of grade Ⅲ AAs. Four cases harbored missense mutations in the EGFR kinase domain (L747A, S768I, V774M, and T790M). A total of 25% of the GBMs showed EGFR amplification. Moreover, 27% of the EGFR mutations occurred in the kinase domain. EGFRvⅢ positivity was detected in 8.0% of EGFR-amplified GBMs. We identified two other EGFR variants in GBM cases with deletions of exons 6–7 (Δe 6-7) (one case) and exons 2–14 (Δe 2-14) (two cases). Interestingly, in one case, the initial EGFRvIII mutation transformed into an EGFR Δe 2-14 mutation during recurrence. The frequency of EGFR alterations in our cohort was lower but the frequency of EGFR mutations in the kinase domain in our cohort was higher than that in The Cancer Genome Atlas and Memorial Sloan Kettering Cancer Center cohorts. Conclusions: We suggested that the EGFR gene profiles of GBM differ among cohorts and identified rare EGFR variants with longitudinal and temporal transformations of EGFRvⅢ.

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Distribution and favorable prognostic implication of genomic EGFR alterations in IDH‐wildtype glioblastoma

et al. 2022

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Background We aimed to evaluate the mutation profile, transcriptional variants, and prognostic impact of the epidermal growth factor receptor ( EGFR ) gene in isocitrate dehydrogenase ( IDH )‐wildtype glioblastomas (GBMs). Methods We sequenced EGFR , evaluated the EGFR splicing profile using a next‐generation sequencing oncopanel, and analyzed the outcomes in 138 grade IV IDH ‐wildtype GBM cases. Results EGFR mutations were observed in 10% of GBMs. A total of 23.9% of the GBMs showed EGFR amplification. Moreover, 25% of the EGFR mutations occurred in the kinase domain. Notably, EGFR alterations were a predictor of good prognosis ( p = 0.035). GBM with EGFR alterations was associated with higher Karnofsky Performance Scale scores ( p = 0.014) and lower Ki‐67 scores ( p = 0.005) than GBM without EGFR alterations. EGFRvIII positivity was detected in 21% of EGFR ‐amplified GBMs. We identified two other EGFR variants in GBM cases with deletions of exons 6–7 (Δe 6–7) and exons 2–14 (Δe 2–14). In one case, the initial EGFRvIII mutation transformed into an EGFR Δe 2–14 mutation during recurrence. Conclusions We found that the EGFR gene profiles of GBM differ among cohorts and that EGFR alterations are good prognostic markers of overall survival in patients with IDH ‐wildtype GBM. Additionally, we identified rare EGFR variants with longitudinal and temporal transformations of EGFRvIII .

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

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 35 publications

References 45 publications

TERT Promoter Alterations in Glioblastoma: A Systematic Review

TERT Promoter Alterations in Glioblastoma: A Systematic Review

Detection of EGFR Mutation Distribution and Transcriptional Variants in IDH-wildtype High-grade Gliomas using a Next-generation Sequencing Oncopanel

Distribution and favorable prognostic implication of genomic EGFR alterations in IDH‐wildtype glioblastoma

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