High‐grade gliomas with isocitrate dehydrogenase wild‐type and 1p/19q codeleted: Atypical molecular phenotype and current challenges in molecular diagnosis

Zheng, Linmao; Zhang, Mengni; Hou, Jing; Gong, Jing; Nie, Ling; Chen, Xueqin; Zhou, Qiao; Chen, Ni

doi:10.1111/neup.12672

Cited by 7 publications

(10 citation statements)

References 17 publications

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“…The polymerase chain reaction (PCR) primers for IDH1 , IDH2 , H3F3A , HIST1H3B , BRAF , and promoter regions of telomerase reverse transcriptase ( TERT ) were designed as previously described. 7 Standard buffer conditions, 50 ng of DNA, and Taq DNA polymerase (TaKaRa, China) were used. The reaction mixture was subjected to an initial denaturation at 95°C for 10 minutes, followed by 35 cycles of amplification (denaturation at 95°C for 30 s, annealing at 56°C for 15 s, and extension at 72°C for 20 s).…”

Section: Methodsmentioning

confidence: 99%

“…DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tumor tissues using a DNA FFPE Tissue Kit (Qiagen, Hilden, Germany). The polymerase chain reaction (PCR) primers for IDH1 , IDH2 , H3F3A , HIST1H3B , BRAF , and promoter regions of telomerase reverse transcriptase ( TERT ) were designed as previously described 7. Standard buffer conditions, 50 ng of DNA, and Taq DNA polymerase (TaKaRa, China) were used.…”

Section: Methodsmentioning

confidence: 99%

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Diffuse Midline Gliomas With Histone H3 K27M Mutation in Adults and Children

Zheng¹,

Gong²,

Yu³

et al. 2022

American Journal of Surgical Pathology

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Diffuse midline glioma, H3 K27M-mutant (H3 K27Mmt DMG), is a rare and highly aggressive tumor that is more common in children than in adults. Few studies have compared the differences between pediatric and adult patients with this rare tumor. We here report our retrospective study of 94 adult and 70 pediatric cases of diffuse midline glioma. Surgical tumor samples were analyzed by routine histopathology and immunohistochemistry for H3 K27M, IDH1 R132H, ATRX, p53, OLIG2, glial fibrillary acidic protein, and Ki-67; Sanger sequencing for hot mutation spots in genes including H3F3A, HIST1H3B, IDH1, IDH2, TERT, and BRAF; and methylation-specific polymerase chain reaction for O 6 -methylguanine DNA methyltransferase promoter methylation. The most frequent anatomic locations in adult and pediatric patients were the thalamus and brainstem, respectively. Molecular profiling revealed higher frequencies of ATRX loss and H3.3 mutation in adult than in pediatric H3 K27M-mt DMGs. TERT promoter mutations and O 6methylguanine DNA methyltransferase promoter methylation were not detected in pediatric patients but were present in a few adult patients. During the follow-up period, 93/122 patients (70.1%) died from the disease, with a median survival time of 10.5 months (range: 1 to 104 mo). Kaplan-Meier analyses demonstrated that the prognosis was better for adult patients than the pediatric cohort (P = 0.0003). Multivariate analyses indicated that patient age, primary tumor size, status of ATRX expression, and Ki-67 index were independent prognosticators. The present study showed that there were differences between adult and pediatric H3 K27M-mt DMGs in terms of the anatomic location of tumor, molecular changes, and prognosis.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Diffuse Midline Gliomas With Histone H3 K27M Mutation in Adults and Children

Zheng¹,

Gong²,

Yu³

et al. 2022

American Journal of Surgical Pathology

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“…Detection of IDH mutations, 1p/19q codeletion, and H3F3A mutations (midline position) are now recommended according to their histologic diagnosis. [4][5][6] Emerging evidence has shown that inclusion of molecular characterization could improve the prognostic and predictive stratification of CNS tumors. [7][8][9] In fact, many key mutations in the TERT, ATRX, TP53, and EGFR genes found in gliomas 10,11 could be used as diagnostic, prognostic, and therapeutic biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Molecular Characterization of Chinese Patients with Glioma by Extensive Next-Generation Sequencing Panel Analysis

Zeng¹,

Wang²,

Li³

et al. 2021

CMAR

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Background Tremendous efforts have been made to explore biomarkers for classifying and grading glioma. However, the majority of the current understanding is based on public databases that might not accurately reflect the Asian population. Here, we investigated the genetic landscape of Chinese glioma patients using a validated multigene next-generation sequencing (NGS) panel to provide a strong rationale for the future classification and prognosis of glioma in this population. Methods We analyzed 83 samples, consisting of 71 initial treatments and 12 recurrent surgical tumors, from 81 Chinese patients with gliomas by performing multigene NGS with an Acornmed panel targeting 808 cancer-related hotspot genes, including genes related to glioma (hotspots, selected exons or complete coding sequences) and full-length SNPs located on chromosomes 1 and 19. Results A total of 76 (91.57%) glioma samples had at least one somatic mutation. The most commonly mutated genes were TP53, TERT, IDH1, PTEN, ATRX , and EGFR . Approximately one-third of cases exhibited more than one copy number variation. Of note, this study identified the amplification of genes, such as EGFR and PDGFRA , which were significantly associated with glioblastoma but had not been previously used for clinical classification (P<0.05). Significant differences in genomic profiles between different pathological subtypes and WHO grade were observed. Compared to the MSKCC database primarily comprised of Caucasians, H3F3A mutations and MET amplifications exhibited higher mutation rates, whereas TERT mutations and EGFR and CDKN2A/B copy number variations presented a lower mutation rate in Chinese patients with glioma (P<0.05). Conclusion Our multigene NGS in the simultaneous evaluation of multiple relevant markers revealed several novel genetic alterations in Chinese patients with glioma. NGS-based molecular analysis is a reliable and effective method for diagnosing brain tumors, assisting clinicians in evaluating additional potential therapeutic options, such as targeted therapy, for glioma patients in different racial/ethnic groups.

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“…Gliomas with IDH1 and IDH2 mutations had a better prognosis than wild-type gliomas ( Cohen et al, 2013 ). 1p19q codeletion represents the combined loss of chromosome 1 (1p) and chromosome 19 (19q) in short arm, which is considered as a genetic marker to predict the response of patients with diffuse glioma to chemotherapy and combined radiotherapy and chemotherapy, and the overall survival time of patients with diffuse glioma is longer ( Louis et al, 2019 ; Zheng et al, 2020 ). In this study, it was found that the mutation probability of NF1 gene in C1 and C2 with worse prognosis was high.…”

Section: Discussionmentioning

confidence: 99%

Establishment of a cell senescence related prognostic model for predicting prognosis in glioblastoma

Wang

Sun

et al. 2022

Front. Pharmacol.

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Background: Glioblastoma (GBM) is highly malignant and has a worse prognosis with age, and next-generation sequencing (NGS) provides us with a huge amount of information about GBM.Materials and Methods: Through the enrichment scores of cell senescence-related pathways, we constructed a consensus matrix and mined molecular subtypes and explored the differences in pathological, immune/pathway and prognostic. Also we identified key genes related to cell senescence characteristics using least absolute shrinkage and selection operator (Lasso) regression and univariate COX regression analysis models. The use of risk factor formats to construct clinical prognostic models also explored the differences in immunotherapy/chemotherapy within the senescence-related signatures score (SRS.score) subgroups. Decision trees built with machine learning to identify the main factors affecting prognosis have further improved the prognosis model and survival prediction.Results: We obtained seven prognostic-related pathways related to cell senescence. We constructed four different molecular subtypes and found patients with subtype C1 had the worst prognosis. C4 had the highest proportion of patients with IDH mutations. 1005 differentially expressed genes (DEGs) were analyzed, and finally 194 Risk genes and 38 Protective genes were obtained. Eight key genes responsible for cell senescence were finally identified. The clinical prognosis model was established based on SRS.score, and the prognosis of patients with high SRS.score was worse. SRS.score and age were the vital risk factors for GBM patients through decision tree model mining.Conclusion: We constructed a clinical prognosis model that could provide high prediction accuracy and survival prediction ability for adjuvant treatment of patients with GBM.

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High‐grade gliomas with isocitrate dehydrogenase wild‐type and 1p/19q codeleted: Atypical molecular phenotype and current challenges in molecular diagnosis

Cited by 7 publications

References 17 publications

Diffuse Midline Gliomas With Histone H3 K27M Mutation in Adults and Children

Diffuse Midline Gliomas With Histone H3 K27M Mutation in Adults and Children

Comprehensive Molecular Characterization of Chinese Patients with Glioma by Extensive Next-Generation Sequencing Panel Analysis

Establishment of a cell senescence related prognostic model for predicting prognosis in glioblastoma

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