medulloblastoma WNT activated

Medulloblastoma, WNT-activated: A Rare and Favorable Type

Medulloblastoma, WNT-activated is the least common type of medulloblastoma, accounting for a small percentage of cases. Despite its rarity, this subtype has a remarkably favorable prognosis, with the vast majority of patients experiencing long-term survival [1].

Characteristics and Definition

WNT-activated medulloblastomas are defined by activating mutations in the WNT/β-catenin signaling pathway, often involving CTNNB1 or germline APC [2]. This molecular signature is distinct from other subtypes of medulloblastoma.

Key Features

• Low-risk profile: Children with residual tumor <1.5 cm² and age <16 years are classified as low-risk WNT-pathway medulloblastoma [3].
• Good overall survivorship: In contrast to non-Wnt MBs, which have intermediate-poor overall survivorship, WNT-activated medulloblastomas exhibit improved survival rates [4].

Symptoms and Presentation

While symptoms can vary, common presentations include headaches, nausea, vomiting, blurred and double vision, extreme sleepiness, confusion, and seizures [5]. Early detection is crucial for effective management.

Molecular Subgroups

Medulloblastoma is divided into four main molecular subgroups: WNT-activated, SHH, Group 3, and Group 4. WNT-activated medulloblastomas are a distinct subgroup with unique biological characteristics [6].

Summary and Implications

In summary, medulloblastoma, WNT-activated is an embryonal tumor originating in the dorsal brainstem characterized by activation of the WNT pathway. Its favorable prognosis and distinct molecular profile make it a critical area of study for improving treatment outcomes and understanding the biology of this disease [9].

References: [1] Oct 14, 2024 — Medulloblastoma, WNT-activated is the least common type of medulloblastoma and has by far the best prognosis... [2] by J Helgager · 2020 · Cited by 7 — WNT-activated medulloblastomas are defined by activating mutations in the WNT/β-catenin signaling pathway (eg, CTNNB1 or germline APC), are... [3] by S Mani · 2023 · Cited by 6 — The currently accepted definition of low-risk WNT-pathway medulloblastoma includes children <16 years of age with residual tumour <1.5 cm² and... [4] by B Manoranjan · 2020 · Cited by 44 — By contrast, non-Wnt MBs are characterized by metastatic disease, increased rates of recurrence, and intermediate-poor overall survivorship. [5] Aug 20, 2024 — What Are the Symptoms of a Medulloblastoma? [6] by S Mani · 2023 · Cited by 6 — Novel biological insights have established that medulloblastoma is a heterogenous disease comprising four broad molecular subgroups - WNT, SHH, ... [9] Feb 25, 2024 — In summary, medulloblastoma, WNT-activated, is an embryonal tumour originating in the dorsal brainstem characterized by activation of the WNT...

Medulloblastoma, specifically the WNT-activated type, is a rare and aggressive form of brain cancer that primarily affects children. The symptoms can be subtle and may not always be immediately apparent. Here are some common signs and symptoms associated with medulloblastoma WNT-activated:

• Morning headaches: These tend to be worse in the morning due to increased intracranial pressure caused by the tumor [4].
• Nausea and vomiting: Some children may experience nausea and vomiting, which can be accompanied by headaches [9].
• Weakness or numbness in the arms and/or legs: This symptom is often related to the tumor's impact on motor function [1].
• Problems with walking: Children with medulloblastoma WNT-activated may exhibit difficulties with coordination, balance, and walking due to the tumor's location in the brainstem [6].
• Increased stumbling and falling: As the tumor grows, it can affect the child's ability to maintain their balance, leading to increased incidents of stumbling and falling [6].
• General co-ordination issues: Children may experience clumsiness and difficulties with general coordination due to the tumor's impact on motor function [6].

It is essential to note that these symptoms can be similar to those experienced by children with other conditions. A proper diagnosis can only be made through a comprehensive medical evaluation, including imaging studies (e.g., MRI) and histopathological examination of tissue samples.

References: [1] Aug 20, 2024 — Medulloblastoma: Diagnosis and Treatment [4] Symptoms often include headache, nausea, and vomiting. These tend to be worse in the morning. [6] What are the symptoms of medulloblastoma? · Problems with walking · Increased stumbling and falling · General co-ordination issues, with increasing clumsiness for ... [9] Symptoms, due to a mass effect from the tumor or to obstructive hydrocephalus, include morning headaches, nausea, vomiting, diplopia (manifestation of sixth ...

Diagnostic Tests for Medulloblastoma, WNT Activated

Medulloblastomas are a type of brain tumor that can be classified into different subgroups based on their genetic characteristics. The WNT-activated subgroup is one such classification.

• MRI with Gadolinium DTPA: MRI (Magnetic Resonance Imaging) with the administration of gadolinium DTPA is considered the diagnostic test of choice for medulloblastoma, including the WNT-activated subgroup [2].
• Imaging and Molecular Characterization: In addition to imaging tests like MRI, molecular characterization of CNS tumors, including medulloblastomas, is becoming increasingly important for both diagnostic clarity and prognostication in neuropathology [5].

Specific Diagnostic Features

For WNT-activated medulloblastomas:

• Immunoreactivity for YAP1: These tumors typically demonstrate immunoreactivity for YAP1 (Yes-associated protein 1) but are immunonegative for GAB1 (Growth factor receptor-bound protein 2) [8].

Additional Diagnostic Considerations

While CTNNB1 mutation testing can be used to identify most WNT-activated cases, it is not always required. Genetic copy number analysis and methylation profiling may also provide valuable information in the diagnosis of medulloblastomas, including those with WNT activation [9].

References: [2] - MRI with gadolinium DTPA for diagnostic test of choice [5] - Molecular characterization of CNS tumors [8] - Immunoreactivity for YAP1 and GAB1 in WNT-activated medulloblastomas [9] - CTNNB1 mutation testing and genetic copy number analysis

Medulloblastoma WNT Activated: Current Drug Treatment Options

Medulloblastoma, a type of brain cancer, has been identified as a candidate for therapy de-escalation based on excellent prognosis in patients with WNT activation [1]. The current standard-of-care (SOC) treatment for WNT-activated medulloblastoma includes surgery, irradiation (XRT), and chemotherapy [3].

Therapeutic Strategies

Several therapeutic strategies have been explored to treat WNT-activated medulloblastoma:

• GSK-3 inhibitor: The small molecule CHIR99021 has been used as a GSK-3 inhibitor to activate the Wnt pathway, which may help in developing a therapeutic strategy for WNT-activated medulloblastoma [2].
• CDK4/6 inhibitors: Combinational treatment comprising CDK4/6 inhibitors such as palbociclib, ribociclib, or abemaciclib together with other agents has been explored to treat WNT-activated medulloblastoma [8].
• Lithium: Lithium has been shown to activate the Wnt pathway and abrogate TP53 mutation-associated radiation resistance in medulloblastoma [9].

Current Research

Recent studies have focused on modifying chemotherapy drugs to offer hope for people with WNT-activated medulloblastoma. For example, a study published in 2024 explored the use of a modified chemotherapy drug that offers new hope for patients with this type of brain cancer [10].

In summary, while there is no single "cure" for WNT-activated medulloblastoma, current research and treatment options suggest that therapy de-escalation may be possible based on excellent prognosis in some cases. Further studies are needed to explore the efficacy of these therapeutic strategies.

References:

[1] L Nobre (2020) - Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent prognosis [1].

[2] B Manoranjan (2020) - To develop a therapeutic strategy employing Wnt activation, we initially used the small molecule GSK-3 inhibitor, CHIR99021, which acts as a Wnt activator [2].

[3] KJ Cohen (2023) - Treatment of wingless (WNT)-activated medulloblastoma (WNT+MB) with surgery, irradiation (XRT), and chemotherapy results in excellent prognosis [3].

[8] H MAIER (2021) - Another approach is following the combinational treatment comprising the CDK4/6 inhibitor palbociclib, ribociclib, or abemaciclib, respectively, together with other agents [8].

[9] H Slika (2024) - WNT activation by lithium abrogates TP53 mutation-associated radiation resistance in medulloblastoma [9].

[10] Aug 20, 2024 - Modifying a Chemotherapy Drug Offers Hope to People with Medulloblastoma [10].

Medulloblastoma, particularly the WNT-activated type, can be challenging to diagnose due to its similarity in presentation with other intracranial diseases. However, there are several key factors that can help differentiate it from other conditions.

Key Features of Medulloblastoma WNT Activated:

• Slow progression: Medulloblastomas, including the WNT-activated type, tend to progress slowly compared to other brain tumors [2].
• Intracranial location: These tumors are typically located within the cranial cavity and can cause a range of symptoms depending on their size and location.
• Genetic mutations: The WNT-activated type is often associated with mutations in the CTNNB1 gene, which plays a crucial role in the Wnt/β-catenin signaling pathway [5].

Differential Diagnosis:

When considering differential diagnoses for medulloblastoma WNT activated, it's essential to consider other slowly progressing intracranial diseases. Some of these conditions include:

• Other types of brain tumors: Such as gliomas or ependymomas, which can also present with slow progression and similar symptoms.
• Intracranial metastases: These are secondary tumors that have spread to the brain from other parts of the body and can mimic the presentation of medulloblastoma.

Clinical Presentation:

The clinical presentation of medulloblastoma WNT activated can vary depending on the size, location, and aggressiveness of the tumor. Common symptoms include:

• Headaches: Due to increased intracranial pressure.
• Weakness or numbness in the arms and/or legs: Resulting from compression of adjacent neural structures.
• Changes in bowel or bladder habits: Caused by compression of the spinal cord.

Imaging Studies:

Imaging studies, such as MRI or CT scans, can help confirm the diagnosis of medulloblastoma WNT activated. These studies can reveal the location and size of the tumor, as well as any associated complications [10].

References:

[1] Moreno DA (2023) - Cited by 2 [2] Mizushima M (2023) [5] Mizushima M (2023) [6] Nobre L (2020) - Cited by 41 [8] Sobocińska AA (2018) [9] Di Giannatale A (2016) - Cited by 10