Cerebellar high-grade gliomas do not present the same molecular alterations as supratentorial high-grade gliomas and may show histone H3 gene mutations

2018 ◽  
Vol 37 (05) ◽  
pp. 209-216 ◽  
Author(s):  
Arnault Tauziède-Espariat ◽  
Raphaël Saffroy ◽  
Mélanie Pagès ◽  
Johan Pallud ◽  
Laurence Legrand ◽  
...  
Keyword(s):  
Histone H3 ◽  
Gene Mutations ◽  
High Grade ◽  
Molecular Alterations ◽  
High Grade Gliomas ◽  
Histone H3 Gene

scholarly journals Low-Grade Gemistocytic Morphology in H3 G34R-Mutant Gliomas and Concurrent K27M Mutation: Clinicopathologic Findings

2020 ◽  
Vol 79 (10) ◽  
pp. 1038-1043
Author(s):  
Meaghan Morris ◽  
Meghan Driscoll ◽  
John W Henson ◽  
Charles Cobbs ◽  
LiQun Jiang ◽  
...  
Keyword(s):  
Histone H3 ◽  
Low Grade ◽  
High Grade ◽  
K27m Mutation ◽  
Gemistocytic Astrocytoma ◽  
First Case ◽  
Clinicopathologic Findings ◽  
Tumor Phenotype ◽  
High Grade Gliomas ◽  
H3 K27m Mutations

Abstract Mutations in histone H3 are key molecular drivers of pediatric and young adult high-grade gliomas. Histone H3 G34R mutations occur in hemispheric high-grade gliomas and H3 K27M mutations occur in aggressive, though histologically diverse, midline gliomas. Here, we report 2 rare cases of histologically low-grade gliomas with gemistocytic morphology and sequencing-confirmed histone H3 G34R mutations. One case is a histologically low-grade gemistocytic astrocytoma with a G34R-mutation in H3F3A. The second case is a histologically low-grade gemistocytic astrocytoma with co-occurring K27M and G34R mutations in HIST1H3B. Review of prior histone H3-mutant gliomas sequenced at our institution shows a divergent clinical and immunohistochemical pattern in the 2 cases. The first case is similar to prior histone H3 G34R-mutant tumors, while the second case most closely resembles prior histone H3 K27M-mutant gliomas. These represent novel cases of sequencing-confirmed histone H3 G34R-mutant gliomas with low-grade histology and add to the known rare cases of G34R-mutant tumors with gemistocytic morphology. Although K27M and G34R mutations are thought to be mutually exclusive, we document combined K27M and G34R mutations in HIST1H3B and present evidence suggesting the K27M-mutation drove tumor phenotype in this dual mutant glioma.

Long survival and therapeutic responses in patient histologically disparate high-grade gliomas demonstrating chromosome 1p loss

2000 ◽  
Vol 92 (6) ◽  
pp. 983-990 ◽  
Author(s):  
Yasushi Ino ◽  
Magdalena C. Zlatescu ◽  
Hikaru Sasaki ◽  
David R. Macdonald ◽  
Anat O. Stemmer-Rachamimov ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Genetic Alterations ◽  
Allelic Loss ◽  
High Grade ◽  
Prognostic Information ◽  
Content Type ◽  
Chromosome 1P ◽  
Oligodendroglial Tumors ◽  
High Grade Gliomas ◽  
Fine Print

Object. Allelic loss of chromosome 1p is a powerful predictor of tumor chemosensitivity and prolonged survival in patients with anaplastic oligodendrogliomas. Chromosome 1p loss also occurs in astrocytic and oligoastrocytic gliomas, although less commonly than in pure oligodendroglial tumors. This observation raises the possibility investigated in this study that chromosome 1p loss might also provide prognostic information for patients with high-grade gliomas with astrocytic components.Methods. The authors report on seven patients with high-grade gliomas composed of either pure astrocytic or mixed astrocytic-oligodendroglial phenotypes, who had remarkable neuroradiological responses to therapy or unexpectedly long survivals. All of the tumors from these seven patients demonstrated chromosome 1p loss, whereas other genetic alterations characteristic of high-grade gliomas (p53 gene mutations, EGFR gene amplification, chromosome 10 loss, chromosome 19q loss, or CDKN2A/p16 deletions) were only found in occasional cases. The authors also assessed the frequency of chromosome 1p loss in a series of anonymous high-grade astrocytoma samples obtained from a tumor bank and demonstrate that this genetic change is uncommon, occurring in only 10% of cases.Conclusions. Although any prognostic importance of chromosome 1p loss in astrocytic or mixed astrocytic—oligodendroglial gliomas can only be determined in larger and prospective series, these findings raise the possibility that some high-grade gliomas with chromosome 1p loss, in addition to pure anaplastic oligodendrogliomas, may follow a more favorable clinical course.

scholarly journals Potential Diagnostic Value of the Differential Expression of Histone H3 Variants between Low- and High-Grade Gliomas

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5261
Author(s):  
Irati Hervás-Corpión ◽  
Andrea Gallardo-Orihuela ◽  
Inmaculada Catalina-Fernández ◽  
Irene Iglesias-Lozano ◽  
Olga Soto-Torres ◽  
...  
Keyword(s):  
Histone H3 ◽  
Diagnostic Value ◽  
Low Grade ◽  
Lower Grade ◽  
High Grade ◽  
Histone H3 Variant ◽  
Genes Encoding ◽  
High Grade Gliomas ◽  
Molecular Patterns ◽  
Canonical Histone

Glioblastoma (GB) is the most aggressive form of glioma and is characterized by poor prognosis and high recurrence despite intensive clinical interventions. To retrieve the key factors underlying the high malignancy of GB with potential diagnosis utility, we combined the analysis of The Cancer Gene Atlas and the REMBRANDT datasets plus a molecular examination of our own collection of surgical tumor resections. We determined a net reduction in the levels of the non-canonical histone H3 variant H3.3 in GB compared to lower-grade astrocytomas and oligodendrogliomas with a concomitant increase in the levels of the canonical histone H3 variants H3.1/H3.2. This increase can be potentially useful in the clinical diagnosis of high-grade gliomas, as evidenced by an immunohistochemistry screening of our cohort and can be at least partially explained by the induction of multiple histone genes encoding these canonical forms. Moreover, GBs showing low bulk levels of the H3.1/H3.2 proteins were more transcriptionally similar to low-grade gliomas than GBs showing high levels of H3.1/H3.2. In conclusion, this study identifies an imbalanced ratio between the H3 variants associated with glioma malignancy and molecular patterns relevant to the biology of gliomas, and proposes the examination of the H3.3 and H3.1/H3.2 levels to further refine diagnosis of low- and high-grade gliomas in future studies.

scholarly journals Pediatric supratentorial high-grade gliomas

2003 ◽  
Vol 14 (2) ◽  
pp. 1-8 ◽  
Author(s):  
Mandeep S. Tamber ◽  
James T. Rutka
Keyword(s):  
Patient Survival ◽  
High Grade ◽  
The Novel ◽  
Improve Patient Survival ◽  
Molecular Alterations ◽  
Novel Approaches ◽  
Aggressive Tumors ◽  
High Grade Gliomas ◽  
Improve Patient

The purpose of this review is to highlight some of the pertinent concepts and controversies surrounding the diagnosis and treatment of pediatric supratentorial high-grade gliomas. Unlike the adult counterparts, pediatric high-grade gliomas are likely derived from distinct cytogenetic and molecular alterations. Surgery has been shown to play a role in extending patient survival. Some success is associated with the provision of chemotherapy. Radiotherapy remains an important adjunct in children older than age 3 years. The challenges involved in improving the poor prognosis of children in whom these very aggressive tumors have been diagnosed will be discussed, as well as some of the novel approaches being investigated to improve patient survival and quality of life.

scholarly journals P14.43 Histone H3F3A and HIST1H3B K27M mutations in pediatric high-grade gliomas: the Florentine experience

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii76-iii77
Author(s):  
M Guidi
Keyword(s):  
Meta Analysis ◽  
Histone H3 ◽  
Histone Variants ◽  
Statistical Correlation ◽  
High Grade ◽  
K27m Mutation ◽  
High Grade Gliomas ◽  
The Difference ◽  
Low Incidence ◽  
Line Of Therapy

Abstract Background Pediatric high- grade gliomas (HGGs) represent a malignancy with a poor survival. The genetic analysis of these entities has identified useful mutations for an improved prognostic framing. The research of mutations in all H3 histone variants (HIST1H3B and H3F3A) could be usefull to define tumors with different prognosis and phenotypes inasmuch they seems to drive two distinct oncogenic programmes. MATERIALS E METHODS We performed a retrospective analysis of pediatric HGGs. We evaluated the type of histone H3 mutated and we performed a meta-analysis comparing our results with literature data. RESULTS We evaluated 41 cases of pediatric HGGs (median age of patients: 7 years old, range: 0–32):): 32 anaplastic astrocytoma (78,5%), 9 glioblastoma multiforme (25,9%), We have researched the K27M mutations in the distinct histone H3 variants (i.e. HIST1H3B and H3F3A). The mutation H3F3A K27M was found in 6 patients instead HIST1H3B K27 mutations was found in a single patient with GBM. All the patients with H3F3A K27M mutation had a progression disease but without statistical correlation (p:0,07). They had a worse prognosis with a median overall survival of 15,5 months (p: 0.0014) versus wild type patients (not reached). H3.3K27M mutation status is a significant predictor of OS with a hazard ratio of 4.499 (p = 0.0001). The patient with HIST1H3B K27 mutation died after first line of therapy. Conclusions Due to the low incidence of the mutation HIST1H3B in our series we can’t define the difference with two variants. However, the research of K27M mutation in HGGs has diagnostic and prognostic role. The role of histone H3 mutated could predict the outcome in HGGs patients and it could give us more informations compared to the clinic and radiological characteristic of the tumors.

Histone H3 K27M mutations in adult cerebellar high-grade gliomas

2017 ◽  
Vol 34 (3) ◽  
pp. 113-119 ◽  
Author(s):  
Satoshi Nakata ◽  
Sumihito Nobusawa ◽  
Tatsuya Yamazaki ◽  
Tadashi Osawa ◽  
Keishi Horiguchi ◽  
...  
Keyword(s):  
Histone H3 ◽  
High Grade ◽  
High Grade Gliomas ◽  
H3 K27m Mutations

scholarly journals Pembrolizumab Activity in Recurrent High-Grade Gliomas with Partial or Complete Loss of Mismatch Repair Protein Expression: A Monocentric, Observational and Prospective Pilot Study

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2283 ◽  
Author(s):  
Giuseppe Lombardi ◽  
Valeria Barresi ◽  
Stefano Indraccolo ◽  
Michele Simbolo ◽  
Matteo Fassan ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mismatch Repair ◽  
Gene Mutations ◽  
Complete Loss ◽  
High Grade ◽  
Repair Protein ◽  
Tumor Mutational Burden ◽  
Diverse Origin ◽  
High Grade Gliomas ◽  
Post Hoc

Introduction: Pembrolizumab demonstrated promising results in hypermutated tumors of diverse origin. Immunohistochemical loss of mismatch repair (MMR) proteins has been suggested as a surrogate of hypermutation in high-grade gliomas (HGG). We evaluated the efficacy and safety of pembrolizumab in relapsing HGGs with immunohistochemical loss of at least 1 MMR protein. Molecular biomarkers of pembrolizumab activity were also analyzed. Methods: Consecutive patients with recurrent HGG and partial or complete loss of MMR protein expression were prospectively enrolled; they received pembrolizumab 200 mg once every 3 weeks until disease progression. The primary endpoint was disease control rate (DCR). Post hoc exploratory analyses included next-generation sequencing to assess tumor mutational burden (TMB), and immunostaining for CD8+ T-cells and CD68+ macrophages. Results: Among 310 HGG patients screened, 13 cases with MMR loss were enrolled: eight glioblastoma, four anaplastic astrocytoma, and one anaplastic oligodendroglioma. Median age was 43 years. DCR was 31%: four patients had stable disease and no patient had complete or partial response. TMB ranged between 6.8 and 23.4 mutations/megabase. Neither TMB nor gene mutations, nor CD8+ T-cell and CD68+ macrophage content, were associated with pembrolizumab activity. Conclusions: pembrolizumab showed no apparent benefit in these patients. No molecular biomarker was found to be associated with pembrolizumab activity.

Gliomas in Children

2018 ◽  
Vol 38 (01) ◽  
pp. 121-130 ◽  
Author(s):  
Dominik Sturm ◽  
Mariella Filbin
Keyword(s):  
Time Windows ◽  
Specific Cell ◽  
Low Grade ◽  
High Grade ◽  
Diagnostic Features ◽  
Biologically Relevant ◽  
Molecular Alterations ◽  
Glial Progenitors ◽  
High Grade Gliomas ◽  
Cns Neoplasms

AbstractGliomas are the most common primary central nervous system (CNS) neoplasms in children and adolescents and are thought to arise from their glial progenitors or stem cells. Although the exact cells of origin for most pediatric gliomas remain to be identified, our current understanding is that specific cell populations during CNS development are susceptible to particular oncogenic events during certain time windows and thus give rise to pediatric gliomas with distinct histological, molecular, and clinical features. These may be roughly segregated into low-grade gliomas (WHO grades I or II; including most mixed glial–neuronal tumors) and high-grade gliomas (WHO grades III or IV) according to their clinical course when untreated, even though this is not yet entirely clear for some of the recently emerging groups. The genetic and epigenetic characterization of pediatric gliomas across ages and histologies has facilitated the delineation of biologically relevant subgroups and have revealed potentially targetable alterations in some of them. This review outlines diagnostic features and molecular alterations in pediatric low- and high-grade gliomas and how the latter might be exploited with future targeted therapeutic strategies.

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