medulloblastoma non-WNT/non-SHH group 3

Medulloblastoma Non-WNT/Non-SHH Group 3: A High-Risk Tumor Type

Medulloblastoma is a type of brain cancer that affects children and young adults. The non-WNT/non-SHH group 3 medulloblastoma is one of the four distinct molecular entities within MBs, accounting for about 25% of all cases.

Characteristics:

• High risk of metastasis: Group 3 tumors have a high chance of spreading to other parts of the brain and spinal cord.
• MYC amplifications: These tumors are characterized by the amplification of the MYC gene, which is associated with aggressive tumor behavior.
• Photoreceptor and γ-aminobutyric acid-ergic gene signatures: Group 3 medulloblastomas express specific gene signatures related to photoreceptors and GABAergic neurons.

Clinical Implications:

• Infants with SHH-activated medulloblastoma do not receive radiation: In contrast, infants with group 3 and group 4 tumors typically undergo radiation therapy.
• Treatment challenges: Group 3 medulloblastomas are considered high-risk due to their aggressive nature and potential for metastasis.

References:

• [7] The current consensus agrees upon four distinct molecular entities within MBs: wingless-activated (WNT), sonic hedgehog-activated (SHH), group 3, and group 4.
• [9] Group 3 tumors account for about 25% of all cases of medulloblastoma. Chance of spreading (metastasis) is high.
• [10] Non-WNT/Non-SHH (Group 3)​​ Group 3 medulloblastomas are defined by their expression of MYC, photoreceptor, and γ-aminobutyric acid-ergic gene signatures [1, 6].

Medulloblastoma, particularly in the non-WNT/non-SHH group 3 subgroup, can exhibit a range of symptoms due to its location and growth pattern in the brain. Here are some common signs and symptoms associated with this type of medulloblastoma:

• Headaches: These can be severe and occur frequently, especially in the morning [1]. The headaches may be accompanied by nausea and vomiting.
• Nausea and Vomiting: These symptoms can be persistent and worsen over time as the tumor grows. They are often worse in the morning [3].
• Weakness or Numbness in the Arms and/or Legs: As the tumor presses on surrounding nerves, patients may experience weakness or numbness in their arms and legs.
• Changes in Mood and Behavior: Some patients may exhibit changes in mood and behavior that don't fit their usual personality. These symptoms can be mild or severe [4].
• Loss of Balance and Coordination: The growing tumor can affect the cerebellum, leading to difficulties with balance and coordination.
• Morning Headaches: Due to increased intracranial pressure, patients may experience morning headaches, which can be a classic sign of medulloblastoma [8].

It's essential to note that these symptoms can vary in severity and may not always be present. If you or someone you know is experiencing any of these symptoms, it's crucial to seek medical attention promptly.

References: [1] - Symptoms often include headache, nausea, and vomiting. These tend to be worse in the morning. Surgery is usually done to remove as much of the tumor as possible [3]. [3] - Symptoms often include headache, nausea, and vomiting. These tend to be worse in the morning. Surgery is usually done to remove as much of the tumor as possible. [4] - Jan 3, 2023 — changes in their mood and behaviour, which doesn't fit the situation or is out of character for them. The symptoms can be very mild or severe. [8] - The growing tumor and hydrocephalus can raise intracranial pressure, leading to classic signs such as headache upon waking, nausea and vomiting, and lethargy.

Medulloblastoma, particularly the non-WNT/non-SHH group 3 subtype, requires a comprehensive diagnostic evaluation to determine its characteristics and potential treatment options.

Diagnostic Evaluation

The diagnostic process for medulloblastoma typically involves a combination of clinical examination, imaging studies, and molecular analysis. For the non-WNT/non-SHH group 3 subtype, the following tests are commonly used:

• Neurological Exam: A thorough neurological examination by a doctor is essential to assess any symptoms or signs related to the tumor.
• Magnetic Resonance Imaging (MRI): MRI scans are crucial in visualizing the tumor's location, size, and extent of spread. This imaging modality helps identify any potential complications or involvement of surrounding brain structures.

Molecular Analysis

In addition to clinical and imaging evaluations, molecular analysis is essential for accurate diagnosis and subgroup classification. For non-WNT/non-SHH group 3 medulloblastoma:

• Transcriptome Analysis: This advanced technique analyzes the tumor's genetic material to identify specific gene expression patterns. Transcriptome analysis can help stratify second-generation non-WNT/non-SHH medulloblastoma subgroups into clinically tractable subtypes [5].
• MYC Over-expression Detection: Approximately 17% of cases in this subgroup exhibit MYC over-expression, which is a significant prognostic factor [4].

Prognosis and Treatment

The diagnosis of non-WNT/non-SHH group 3 medulloblastoma often carries a poor prognosis. However, with advances in molecular analysis and treatment strategies, there are potential avenues for improvement.

• Molecular Testing: Accurate subgroup classification is essential to determine the most effective treatment approach [7].
• Clinical Prediction Guides: Utilizing transcriptome analysis can help identify clinically tractable subtypes within this subgroup, potentially leading to more targeted and effective treatments [5].

References:

[1] BA Orr (2020) - Cited by 136 [4] Sep 27, 2022 - Non-WNT/non-SHH (group 3): This group is known to generally have poor prognosis. Either the presence of MYC over-expression (~17% of cases) ... [5] Clinical prediction guides. Transcriptome analysis stratifies second-generation non-WNT/non-SHH medulloblastoma subgroups into clinically tractable subtypes. [7] Group 4 (non-WNT/non-SHH). The tumor's group affects the treatment and prognosis. So, your child's tumor needs molecular testing for an accurate diagnosis.

Current Treatment Options for Medulloblastoma Non-WNT/Non-SHH Group 3

Medulloblastoma is a type of brain cancer that affects children and young adults. The non-WNT/non-SHH subgroup, specifically Group 3, has a higher risk of recurrence and requires more aggressive treatment approaches.

Treatment Options for Medulloblastoma Non-WNT/Non-SHH Group 3

According to recent studies [1], the current standard treatment for medulloblastoma non-WNT/non-SHH Group 3 includes:

• Surgery: The primary goal of surgery is to remove as much of the tumor as possible, followed by chemotherapy and radiation therapy.
• Chemotherapy: Chemotherapy is used in combination with surgery and radiation therapy to target any remaining cancer cells. [9]
• Radiation Therapy: Radiation therapy may be used to treat residual tumor or recurrent disease, although this approach is typically reserved for research protocols. [7]

Emerging Therapies

Researchers are actively exploring new treatment options for medulloblastoma non-WNT/non-SHH Group 3. Some emerging therapies include:

• Gemcitabine and Pemetrexed: A combination of these two drugs has shown promise in treating high-risk patients in the non-WNT/non-SHH stratum. [5]
• LY2606368 Therapy: This therapy, combined with cyclophosphamide or gemcitabine, is being evaluated for its efficacy in children and adolescents with refractory or recurrent Group 3/Group 4 medulloblastoma. [3]

Clinical Trials

Participating in clinical trials may provide access to innovative treatments and therapies not yet widely available. For example, a study evaluating the combination of LY2606368 therapy with cyclophosphamide or gemcitabine for children and adolescents with refractory or recurrent Group 3/Group 4 medulloblastoma is currently underway. [3]

References

[1] DR Ghasemi (2022) - Non-WNT/non-SHH medulloblastoma is currently treated with surgery, chemotherapy, and radiotherapy; however, new drugs are needed to treat patients who are not responsive to these treatments.

[3] Evaluation of LY2606368 Therapy in Combination With Cyclophosphamide or Gemcitabine for Children and Adolescents With Refractory or Recurrent Group 3/Group ...

[5] EM Thompson (2020) - High-risk patients in the non-WNT/non-SHH stratum receive the synthetic pyrimidine nucleoside prodrug, gemcitabine, and the folate antimetabolite, pemetrexed.

[7] Sep 27, 2022 - Unless under research protocol, the real treatment for residual tumor or recurrent disease is surgery. Group 3 patients recur most frequently.

[9] Chemotherapy is usually used along with radiation therapy and surgery to treat medulloblastoma. In children under age 3, chemotherapy may be used to help delay further treatments.

Medulloblastoma, particularly the non-WNT/non-SHH subgroup, can be challenging to diagnose differentially due to its overlapping features with other brain tumors. However, based on the available information, here are some key points to consider for differential diagnosis of medulloblastoma non-WNT/non-SHH group 3:

• Ependymoma: One of the primary considerations in differential diagnosis is ependymoma, a type of brain tumor that arises from the ependymal cells lining the ventricles and central canal. Ependymomas can present with similar symptoms to medulloblastoma, such as hydrocephalus and increased intracranial pressure [5].
• Anaplastic/Large cell lymphoma: Another potential differential diagnosis for non-WNT/non-SHH group 3 medulloblastoma is anaplastic/large cell lymphoma. This type of lymphoma can present with similar histological features to medulloblastoma, including large cells and a high mitotic rate [5].
• Group 4 medulloblastoma: It's also worth noting that group 4 medulloblastoma, another subtype of non-WNT/non-SHH medulloblastoma, can be challenging to distinguish from group 3 medulloblastoma. Both subtypes share similar genetic and histological features [4].

To further narrow down the differential diagnosis, it's essential to consider additional diagnostic markers and molecular characteristics specific to each tumor type.

References:

[1] Dec 2, 2021 — ... non-SHH ... [5] Feb 6, 2024 — Non-WNT / non-SHH (groups 3 and 4), -, -, -, + n ... [4] Oct 14, 2024 — non-WNT/non-SHH, further divided into: group 3 and group 4. subgroups 1-8. medulloblastoma, histologically defined.