H3G34-Mutant Gliomas—A Review of Molecular Pathogenesis and Therapeutic Options

Nguyen, Anthony; Soto, Jose M.; Gonzalez, Sarah-Marie; Murillo, Jennifer; Trumble, Eric R.; Shan, Frank Y.; Huang, Jason H.

doi:10.3390/biomedicines11072002

Cited by 5 publications

(5 citation statements)

References 143 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Embryonal tumor morphology is a pattern of some H3G34-altered DHGs. They also tend to be tumors seen in older children or early adulthood, which is not a characteristic of our group 23 . According to Yeo et al, 24 there could be 9% IDH mutant adult-type gliomas in our study, but that does not affect the importance of the MMR status of the tumors.…”

Section: Discussionmentioning

confidence: 46%

“…They also tend to be tumors seen in older children or early adulthood, which is not a characteristic of our group. 23 According to Yeo et al, 24 there could be 9% IDH mutant adult-type gliomas in our study, but that does not affect the importance of the MMR status of the tumors. Suwala et al 25 have suggested that primary dMMR IDH mutant astrocytoma have the worst clinical outcome.…”

Section: Discussionmentioning

confidence: 48%

See 1 more Smart Citation

Immunohistochemical Approach to Mismatch Repair Deficiency in Pediatric High-Grade Glioma

Inan,

Ogut,

Toker

et al. 2024

Applied Immunohistochemistry &Amp; Molecular Morphology

View full text Add to dashboard Cite

Knowledge of the molecular pathways of pediatric high-grade gliomas is increasing. Gliomas with mismatch repair deficiency do not currently comprise a distinct group, but data on this topic have been accumulating in recent publications. Immunohistochemistry can effectively determine mismatch repair status, indirectly suggesting the microsatellite instability of the tumor. This study aimed to determine the number of mismatch repair-deficient pediatric high-grade gliomas in a tertiary institution and assess the relationship between the survival and mismatch repair status of the patients. It also aimed to assess the potential for further clinical studies including immunotherapy. Of 24 patients with high-grade gliomas, 3 deceased patients were mismatch repair-deficient. Mismatch repair deficiency was significantly associated with shorter survival (P=0.004). Immunotherapy trials need to progress, and patients with mismatch repair-deficient pediatric high-grade gliomas are the most suitable candidates for such studies.

show abstract

Section: Discussionmentioning

confidence: 46%

Section: Discussionmentioning

confidence: 48%

Immunohistochemical Approach to Mismatch Repair Deficiency in Pediatric High-Grade Glioma

Inan,

Ogut,

Toker

et al. 2024

Applied Immunohistochemistry &Amp; Molecular Morphology

View full text Add to dashboard Cite

show abstract

“…This study revealed that ONC201 disrupts integrated metabolic and epigenetic pathways, leading to a reversal of pathognomonic H3K27me3 reduction [ 93 , 102 ]. In the G34R/V mutation, it has been shown that it does not directly participate in the methylation of G34, but affects the methylation of the adjacent K36 (H3 K36me2/3) [ 150 ]; however, unlike K27M, the manner in which G34R/V exerts its dominant effect on H3 biology and results in tumorigenesis remains to be elucidated [ 151 ].…”

Section: Clinical Practice and Molecular Markermentioning

confidence: 99%

Liquid Biopsy for Glioma Using Cell-Free DNA in Cerebrospinal Fluid

Otsuji,

Fujioka,

Hata

et al. 2024

Cancers

View full text Add to dashboard Cite

Glioma is one of the most common primary central nervous system (CNS) tumors, and its molecular diagnosis is crucial. However, surgical resection or biopsy is risky when the tumor is located deep in the brain or brainstem. In such cases, a minimally invasive approach to liquid biopsy is beneficial. Cell-free DNA (cfDNA), which directly reflects tumor-specific genetic changes, has attracted attention as a target for liquid biopsy, and blood-based cfDNA monitoring has been demonstrated for other extra-cranial cancers. However, it is still challenging to fully detect CNS tumors derived from cfDNA in the blood, including gliomas, because of the unique structure of the blood–brain barrier. Alternatively, cerebrospinal fluid (CSF) is an ideal source of cfDNA and is expected to contribute significantly to the liquid biopsy of gliomas. Several successful studies have been conducted to detect tumor-specific genetic alterations in cfDNA from CSF using digital PCR and/or next-generation sequencing. This review summarizes the current status of CSF-based cfDNA-targeted liquid biopsy for gliomas. It highlights how the approaches differ from liquid biopsies of other extra-cranial cancers and discusses the current issues and prospects.

show abstract

“…The epidemiology of diffuse hemispheric glioma with H3 G34 mutation shows a slight male predominance and a typically more aggressive course than other pediatric brain tumors [ 119 ]. This mutation is less common than the H3 K27M mutation found in midline gliomas, with specific genetic and clinical features that differentiate them from other glioma subtypes [ 121 ].…”

Section: Diffuse Hemispheric Glioma H3 G34-mutantmentioning

confidence: 99%

“…Driving mutation here is a missense mutation of the H3F3A gene, eventually causing glycine 34 to be replaced by arginine or valine in the mature protein [ 121 ]. While G34 is not subject to methylation, this particular mutation leads to changes that inhibit binding of regulatory proteins and ultimately causes transcriptional reprograming [ 3 , 105 ].…”

Section: Diffuse Hemispheric Glioma H3 G34-mutantmentioning

confidence: 99%

The 2021 World Health Organization Central Nervous System Tumor Classification: The Spectrum of Diffuse Gliomas

Gue,

Lakhani

2024

Biomedicines

View full text Add to dashboard Cite

The 2021 edition of the World Health Organization (WHO) classification of central nervous system tumors introduces significant revisions across various tumor types. These updates, encompassing changes in diagnostic techniques, genomic integration, terminology, and grading, are crucial for radiologists, who play a critical role in interpreting brain tumor imaging. Such changes impact the diagnosis and management of nearly all central nervous system tumor categories, including the reclassification, addition, and removal of specific tumor entities. Given their pivotal role in patient care, radiologists must remain conversant with these revisions to effectively contribute to multidisciplinary tumor boards and collaborate with peers in neuro-oncology, neurosurgery, radiation oncology, and neuropathology. This knowledge is essential not only for accurate diagnosis and staging, but also for understanding the molecular and genetic underpinnings of tumors, which can influence treatment decisions and prognostication. This review, therefore, focuses on the most pertinent updates concerning the classification of adult diffuse gliomas, highlighting the aspects most relevant to radiological practice. Emphasis is placed on the implications of new genetic information on tumor behavior and imaging findings, providing necessary tools to stay abreast of advancements in the field. This comprehensive overview aims to enhance the radiologist’s ability to integrate new WHO classification criteria into everyday practice, ultimately improving patient outcomes through informed and precise imaging assessments.

show abstract

H3G34-Mutant Gliomas—A Review of Molecular Pathogenesis and Therapeutic Options

Cited by 5 publications

References 143 publications

Immunohistochemical Approach to Mismatch Repair Deficiency in Pediatric High-Grade Glioma

Immunohistochemical Approach to Mismatch Repair Deficiency in Pediatric High-Grade Glioma

Liquid Biopsy for Glioma Using Cell-Free DNA in Cerebrospinal Fluid

The 2021 World Health Organization Central Nervous System Tumor Classification: The Spectrum of Diffuse Gliomas

Contact Info

Product

Resources

About