scholarly journals Invited Review: Emerging functions of histone H3 mutations in paediatric diffuse high‐grade gliomas

2020 ◽  
Vol 46 (1) ◽  
pp. 73-85 ◽  
Author(s):  
L. H. Kasper ◽  
S. J. Baker
Keyword(s):  
Histone H3 ◽  
High Grade ◽  
High Grade Gliomas

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.

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.

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 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

Venous Thromboembolism and High Grade Gliomas

1993 ◽  
Vol 70 (03) ◽  
pp. 393-396 ◽  
Author(s):  
Mandeep S Dhami ◽  
Robert D Bona ◽  
John A Calogero ◽  
Richard M Hellman
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Medical Center ◽  
Significant Risk ◽  
Bleeding Complications ◽  
Fisher Exact Test ◽  
High Grade ◽  
Chi Square ◽  
Exact Test ◽  
High Grade Gliomas

SummaryA retrospective study was done to determine the incidence of and the risk factors predisposing to clinical venous thromboembolism (VTE) in patients treated for high grade gliomas. Medical records of 68 consecutive patients diagnosed and treated at Saint Francis Hospital and Medical Center from January 1986 to June 1991 were reviewed. The follow up was to time of death or at least 6 months (up to December 1991). All clinically suspected episodes of VTE were confirmed by objective tests. Sixteen episodes of VTE were detected in 13 patients for an overall episode rate of 23.5%. Administration of chemotherapy (p = 0.027, two tailed Fisher exact test) and presence of paresis (p = 0.031, two tailed Fisher exact test) were statistically significant risk factors for the development of VTE. Thrombotic events were more likely to occur in the paretic limb and this difference was statistically significant (p = 0.00049, chi square test, with Yates correction). No major bleeding complications were seen in the nine episodes treated with long term anticoagulation.We conclude that venous thromboembolic complications are frequently encountered in patients being treated for high grade gliomas and the presence of paresis and the administration of chemotherapy increases the risk of such complications.

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