diffuse midline glioma, H3 K27M-mutant

Diffuse Midline Glioma, H3 K27M-Mutant: A Rare and Aggressive Tumor

Diffuse midline glioma, H3 K27M-mutant (H3 K27M-mt DMG) is a rare and highly aggressive type of brain tumor that primarily affects children and adolescents. However, it can also occur in adults.

Characteristics and Prognosis

• Aggressive nature: H3 K27M-mt DMG is considered a highly invasive tumor with a poor prognosis.
• Rare occurrence: This type of tumor is relatively rare compared to other types of brain tumors.
• Specific mutations: The presence of specific mutations in the H3F3A gene is a key characteristic of diffuse midline gliomas, including H3 K27M-mt DMG.

Key Facts

• Diffuse midline glioma, H3 K27M-mutant primarily manifests in children and adolescents [6].
• These tumors are highly aggressive and classified as a WHO Grade IV tumor regardless of histopathologic features [1].
• Some diffuse midline gliomas have changes in histone-related genes, with the most common gene being h3K27M [4].

References

[1] AM Bhattarai (2022) - Diffuse midline glioma with H3 K27M mutation is highly aggressive and classified as a WHO Grade IV tumor regardless of histopathologic features. [2] L Zheng (2022) - Diffuse midline glioma, H3 K27M-mutant (H3 K27M-mt DMG), is a rare and highly aggressive tumor that is more common in children than in adults. [4] Aug 20, 2024 - Some diffuse midline gliomas have changes in histone-related genes. The most common gene is h3K27M. [6] Z Yang (2024) - Diffuse midline gliomas with H3K27 M mutation primarily manifest in children and adolescents, and can also occur in adults.

Common Signs and Symptoms of Diffuse Midline Glioma (H3 K27M-mutant)

Diffuse midline gliomas are rare brain tumors that can cause a range of symptoms. While the exact signs and symptoms may vary from person to person, here are some common ones associated with H3 K27M-mutant diffuse midline glioma:

• Headaches: One of the most frequent complaints among children with diffuse midline glioma is headaches [9].
• Seizures: Seizures can occur in some cases, especially if the tumor is located near the brain's seizure-prone areas [8].
• Weakness or numbness: Weakness or numbness in the face, arm, or leg may be experienced due to the tumor's location and pressure on surrounding nerves.
• Vision problems: In some cases, vision problems such as blurred vision, double vision, or loss of vision can occur if the tumor is located near the optic nerve.

Important Note

It's essential to note that not everyone with diffuse midline glioma will experience all these symptoms. The severity and type of symptoms can vary greatly from person to person. If you suspect someone has this condition, it's crucial to consult a medical professional for an accurate diagnosis and treatment plan.

References:

[8] Jun 18, 2016 — ... mutations define two subgroups of diffuse intrinsic pontine gliomas with different ... Sign in ... Diffuse midline glioma - H3 K27M–mutant ...

[9] Signs & symptoms. Column 1. Children · Headaches ... Having an HIST1H3B mutation/not having the H3 K27M mutation ... Read more about diffuse midline glioma symptoms ...

Diagnostic Tests for Diffuse Midline Glioma (DMG), H3 K27M-mutant

Diffuse midline gliomas (DMGs) are rare and serious tumors in the brain and spinal cord. The diagnosis of DMG, specifically the H3 K27M-mutant type, can be challenging but is crucial for effective treatment. Here are some diagnostic tests used to identify this condition:

• Hematoxylin and Eosin (H&E) Staining: This is a standard histopathological test that helps confirm tissue diagnosis of glioma and WHO-grade [1].
• Immunohistochemistry (IHC): IHC is an effective and rapid detection method for identifying the H3K27M mutation in pathology laboratories [3]. It involves using antibodies to detect specific proteins associated with the mutation.
• Polymerase Chain Reaction (PCR) Amplification: PCR amplification of a DNA fragment can verify H3K27M IHC results, providing further confirmation of the mutation [1].
• Magnetic Resonance Imaging (MRI): MRI is often used to diagnose DMG and assess its location and extent. It can help identify the tumor's characteristics, such as its size, shape, and position in the brain or spinal cord [8].
• Clinical Presentation and Neuroimaging Studies: Clinical presentation, neuroimaging studies like MRI, and sometimes confirmed through IHC are used to diagnose DMGs [8].

References:

[1] by T Huang · 2018 · Cited by 64 — Hematoxylin and Eosin staining was used to confirm tissue diagnosis of glioma and of WHO-grade. H3K27M IHC results were verified via PCR-amplification of a ...

[3] by H Zhao · 2020 · Cited by 8 — This study demonstrated that IHC is an effective and rapid detection method for routine use in pathology laboratories for the identification of H3K27M mutation.

[8] by S Al Sharie · 2023 · Cited by 9 — DMGs are typically diagnosed based on clinical presentation, neuroimaging studies such as magnetic resonance imaging (MRI), and sometimes confirmed through ...

Note: The above information is a summary of the diagnostic tests used to identify diffuse midline glioma, H3 K27M-mutant.

Current Treatment Options for Diffuse Midline Glioma (H3 K27M-mutant)

Diffuse midline gliomas (DMGs) are rare and aggressive brain tumors that can occur in both children and adults. The H3 K27M mutation is a specific genetic alteration found in these tumors, which makes treatment challenging.

Surgery

The first line of treatment for DMG is surgery, if possible. The goal of surgery is to obtain tissue for diagnosis and potentially relieve pressure on the brain (6). However, surgery alone may not be sufficient to control the tumor growth.

Chemotherapy

Chemotherapy drugs such as temozolomide have been used to treat adult high-grade gliomas, but their effectiveness in H3 K27M-mutant DMG is limited. Unfortunately, chemotherapy has shown minimal benefit for patients with this specific mutation (8).

Experimental Therapies

Recent studies have explored the potential of experimental therapies, such as:

• Panobinostat: A general histone deacetylase inhibitor that has shown good in vitro efficacy against DIPG tumors harboring the H3K27M mutation (3 and 5).
• Dordaviprone: An experimental drug that shows promise for treating aggressive H3 K27M-mutant DMGs, offering hope to patients with limited treatment options (4).

CAR T-cell Therapy

A recent study has demonstrated the efficacy of GD2-targeted CAR T-cell therapy in treating H3K27M-mutant DIPG. This approach precisely targets tumor cells, improving efficacy and reducing side effects (1 and 7). However, more research is needed to confirm these findings.

Current Standard of Care

Unfortunately, there is currently no effective treatment for H3 K27M-mutant DMG. The standard of care remains radiotherapy, as systemic therapies have not proven to be effective (10).

It's essential to note that the prognosis for patients with H3 K27M-mutant DMG remains poor, and further research is necessary to develop more effective treatment options.

References:

1. Z Yang · 2024 · Cited by 4
2. St.
3. BT Himes · 2019 · Cited by 114
4. Mar 1, 2024
5. BT Himes · 2019 · Cited by 114
6. Aug 20, 2024
7. Z Yang · 2024 · Cited by 4
8. Diffuse midline glioma treatment ... H3.3 K27M mutation or not.
9. by M van den Bent · 2024 · Cited by 3
10. Feb 14, 2024

Diffuse Midline Glioma (DMG), H3 K27M-mutant Differential Diagnosis

Diffuse midline gliomas (DMGs) are a type of brain tumor characterized by the presence of specific mutations in the H3F3A gene, leading to the H3 K27M mutation. The differential diagnosis for DMG, H3 K27M-mutant involves considering other high-grade glioma subtypes that may present with similar clinical and radiological features.

Key Considerations:

• Other High-Grade Gliomas: Other high-grade gliomas, such as anaplastic astrocytomas or glioblastomas, can be considered in the differential diagnosis of DMG, H3 K27M-mutant. These tumors may also present with similar clinical and radiological features, including rapid growth and infiltration into surrounding brain tissue.
• H3F3A Wild-Type Tumors: Some high-grade gliomas may not harbor the H3 K27M mutation but still exhibit aggressive behavior and similar histopathological features to DMG, H3 K27M-mutant. These tumors are often referred to as "H3 wild-type" or "H3F3A wild-type" gliomas.
• Additional Mutations: The presence of additional mutations, such as FGFR1 hotspot point mutations (N546K and K656E), can also be considered in the differential diagnosis of DMG, H3 K27M-mutant. These mutations may contribute to the development or progression of high-grade gliomas.

Diagnostic Approaches:

• Histopathological Examination: A neuropathologist should confirm the diagnosis by examining histopathological sections of the tumor.
• Genetic Testing: Genetic testing can be performed to identify specific mutations, including H3 K27M and other high-grade glioma-associated mutations.
• Imaging Studies: Imaging studies, such as MRI or CT scans, may also be used to evaluate the extent of tumor infiltration and guide diagnostic approaches.

References:

• [1] The most common gene is h3K27M. A neuropathologist should confirm the diagnosis. Do Diffuse Midline Gliomas Spread? Diffuse midline gliomas are ...
• [5] by L Zheng · 2022 · Cited by 51 — Sanger sequencing showed that the tumor harbored H3 K27M mutation in the H3F3A gene which confirmed the diagnosis of diffuse midline glioma, H3 K27M-mutant, WHO ...
• [8] Another key characteristic of diffuse midline gliomas is the presence of specific mutations in the H3F3A gene; these tumors are described as “H3 K27M-mutant.
• [10] by N Hayashi · 2024 · Cited by 2 — A recent comprehensive genomic study of H3F3A-mutant high-grade gliomas revealed that FGFR1 hotspot point mutations (N546K and K656E) were ...