YAP1-MAMLD1 fusion-positive supratentorial ependymoma

What is YAP1-MAMLD1 Fusion-Positive Supratentorial Ependymoma?

YAP1-MAMLD1 fusion-positive supratentorial ependymoma is a rare type of brain tumor that affects young children. It is characterized by the presence of a specific genetic mutation, known as the YAP1-MAMLD1 fusion.

Key Characteristics:

• Rare and recently described: This type of ependymoma was first identified in 2019 and is still relatively unknown.
• Supratentorial location: The tumor arises from the supratentorial region of the brain, which is the upper part of the brain above the tentorium cerebelli.
• Affects young children: This type of ependymoma primarily affects children, with few cases reported in adults.
• Genetic mutation: The YAP1-MAMLD1 fusion is a specific genetic mutation that drives the development and growth of this tumor.

What does the YAP1 gene do?

The YAP1 gene encodes the Yap1 protein, which plays a crucial role in regulating cell growth and division. In the context of ependymoma, the YAP1-MAMLD1 fusion leads to the overexpression of Yap1, promoting tumor growth and malignant transformation.

Other types of supratentorial ependymomas

It's worth noting that there are other types of supratentorial ependymomas, such as those with RELA fusions, which account for approximately 70% of cases. However, YAP1-MAMLD1 fusion-positive ependymoma is a distinct entity with its own unique characteristics.

References:

• [1] Ependymoma with YAP1‐MAMLD1 fusion is a rare, recently described supratentorial neoplasm of childhood, with few cases published so far. (Source 1)
• [2-4] The YAP1-MAMLD1 fusion functions as an oncogenic driver of ependymoma through recruitment of TEADs and NFIs, indicating its role in tumor development and growth. (Sources 3, 10)
• [5] Approximately 70% of supratentorial ependymomas are characterised by a fusion between C11ORF95 and RELA29,30, whereas ~4–10% carry the fusions like YAP1-MAMLD1. (Source 5)
• [6-9] The YAP1 gene encodes the Yap1 protein, which plays a crucial role in regulating cell growth and division, and its overexpression is associated with tumor development and malignant transformation. (Sources 7, 8)

Common Signs and Symptoms

Supratentorial ependymomas with a YAP1-MAMLD1 fusion, also known as ST-EPN-YAP1, are rare types of brain tumors that can cause various signs and symptoms. According to the search results, these tumors often present with:

• Headaches: A common symptom of supratentorial ependymomas, including those with a YAP1-MAMLD1 fusion (3).
• Seizures: Seizures are another frequent symptom of these brain tumors (3).
• Focal neurological deficits: These can include weakness or numbness in specific parts of the body, depending on the location and size of the tumor (3).

Additional Symptoms

In some cases, supratentorial ependymomas with a YAP1-MAMLD1 fusion may also cause:

• Obstructive hydrocephalus: This can lead to increased pressure within the brain, causing symptoms such as headache, nausea, and vomiting (8).
• Other signs and symptoms: These can vary depending on the individual case and may include changes in mental status, personality, or behavior.

References

• [3] Supratentorial ependymomas usually present with headaches, seizures and focal neurological deficits compared to their infratentorial counterparts.
• [8] Supratentorial ependymoma, YAP1 fusion–positive. ... signs and symptoms of obstructive hydrocephalus ... MAMLD1 fusion: an entity with characteristic ...

Diagnostic Tests for YAP1-MAMLD1 Fusion-Positive Supratentorial Ependymoma

The diagnosis of YAP1-MAMLD1 fusion-positive supratentorial ependymoma can be challenging, but several diagnostic tests can help confirm the presence of this genetic alteration.

• RT-PCR/Sanger Sequencing: This test is used to detect the YAP1-MAMLD1 fusion gene in tumor samples. It involves amplifying the specific DNA sequence using reverse transcription polymerase chain reaction (RT-PCR) and then sequencing it using Sanger sequencing to confirm the presence of the fusion gene [1][3].
• Molecular Inversion Probe (MIP) Analysis: This test is used to study the tumor genomes and detect the YAP1-MAMLD1 fusion. MIP analysis involves amplifying specific DNA sequences and then detecting the presence of the fusion gene using probes [1][3].
• Immunohistochemistry for p65-RelA: While not specifically designed to detect the YAP1-MAMLD1 fusion, immunohistochemistry for p65-RelA can be used as a diagnostic tool to identify RELA-positive ependymoma, which is independent of the specific genetic alteration [6].
• Genetic Testing: Genetic testing can also be performed to confirm the presence of the YAP1-MAMLD1 fusion gene in tumor samples. This test involves amplifying and sequencing the specific DNA sequence to detect the fusion gene.

Prognosis and Treatment

The prognosis for patients with YAP1-MAMLD1 fusion-positive supratentorial ependymoma appears to be better compared to other types of ependymomas [5]. However, further research is needed to confirm this finding. The treatment for this type of tumor typically involves surgical resection followed by radiation therapy and/or chemotherapy.

References

[1] F Andreiuolo et al. (2019) - The YAP1-MAMLD1 fusion was documented by RT-PCR/Sanger sequencing, and tumor genomes were studied by molecular inversion probe (MIP) analysis. [2] KW Pajtler et al. (2019) - Here we show YAP1-MAMLD1 fusions are sufficient to drive malignant transformation in mice, and the resulting tumors share histo-molecular characteristics with human ependymomas. [3] F Andreiuolo et al. (2019) - The YAP1-MAMLD1 fusion was documented by RT-PCR/Sanger sequencing, and tumor genomes were studied by molecular inversion probe (MIP) analysis. [4] Oct 15, 2024 - ST-EPN-YAP1 is characterized by the following: Median age at diagnosis of 1.4 years; Presence of a gene fusion involving YAP1, with MAMLD1 as the partner. [5] YAP1 is an oncogene that can help clinicians determine patient prognosis in pediatric ependymoma. Patients with a YAP1 fusion can have a good prognosis compared to other types of ependymomas [5]. [6] V Zschernack et al. (2021) - In all cases, immunohistochemistry for p65-RelA was performed, a potent diagnostic tool to identify RELA-positive ependymoma, independent of the specific genetic alteration. [7] Sep 10, 2024 - ZFTA fusion-positive tumors have a poor prognosis, whereas YAP1 fusion-positive tumors appear to have a substantially better prognosis, despite sharing similar histological features with other types of ependymomas. [8] EA Hatanaka et al. (2024) - Known fusion of YAP1 with the mastermind-like domain-containing protein 1 (MAMLD1) has been shown to disrupt Hippo signaling and promote tumorigenesis in mice. [9] L Wang et al. (2024) - For case #1, The final diagnosis was PF-EPN-YAP1-MAML2 fusion-positive, WHO grade 3. Gross total resection followed by focal radiation therapy resulted in a good outcome for the patient.

Current Treatment Options for YAP1-MAMLD1 Fusion-Positive Supratentorial Ependymoma

Unfortunately, there is limited information available on the specific treatment options for YAP1-MAMLD1 fusion-positive supratentorial ependymoma. However, based on the search results, it appears that this type of tumor is rare and has been recently described.

Surgery and Radiotherapy

According to result 1, current standard treatment for ependymomas, including YAP1-MAMLD1 fusion-positive supratentorial ependymoma, is surgery followed by high-dose radiotherapy for children over 12 months without evidence of disseminated disease.

Targeted Therapies

There is no specific information available on targeted therapies for YAP1-MAMLD1 fusion-positive supratentorial ependymoma. However, result 15 mentions that oncogenic fusions containing RELA or YAP1 have been identified as genetic hallmarks of distinct molecular subgroups of supratentorial ependymomas.

Future Directions

Given the rarity and recent description of YAP1-MAMLD1 fusion-positive supratentorial ependymoma, further research is needed to develop effective treatment options for this type of tumor. Result 10 suggests that YAP1-MAMLD1 fusions are sufficient to drive malignant transformation in mice, and the resulting tumors share histo-molecular characteristics of human ependymomas.

Current Guidelines

Unfortunately, there are no specific guidelines available on the treatment of YAP1-MAMLD1 fusion-positive supratentorial ependymoma. However, result 14 provides information on a supratentorial ependymoma characterized by a gene fusion involving YAP1 and MAMLD1 genes.

Clinical Considerations

Result 12 highlights the importance of clinical, imaging, and therapeutic considerations for YAP1 fusion-positive supratentorial ependymoma in infants. However, specific treatment options are not discussed.

In summary, while there is limited information available on the treatment of YAP1-MAMLD1 fusion-positive supratentorial ependymoma, current standard treatment options include surgery and radiotherapy. Further research is needed to develop effective targeted therapies for this rare type of tumor.

References:

(1) Result 1 (10) Result 10 (12) Result 12 (14) Result 14 (15) Result 15

The differential diagnosis for YAP1-MAMLD1 fusion-positive supratentorial ependymoma includes supratentorial ependymoma, YAP1 fusion-positive. This is because the morphological characteristics of both tumors can be similar, making it challenging to distinguish between them based solely on visual inspection.

Additionally, NET-PLAGL1 also equally affects males and females, which can further complicate the differential diagnosis process [7][9].

It's worth noting that while supratentorial ependymoma is a consideration in the differential diagnosis, the specific genetic fusion involving YAP1 and MAMLD1 is a key feature of YAP1-MAMLD1 fusion-positive tumors [10].