Molecular Ependymoma Illustration

Beyond the Microscope: Unlocking the Secrets of Ependymoma Through Molecular Insights

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Kai Mendoza in Health & Wellness November 2025 • 4 min read.

"Discover how advancements in molecular biology are transforming our understanding of ependymoma, paving the way for targeted treatments and improved outcomes."


Ependymoma (EPN) is a tumor of the central nervous system that affects both children and adults. In children, these tumors typically arise in the brain, either above the tentorium cerebelli (supratentorial) or in the posterior fossa, which includes the cerebellum and brainstem. Spinal ependymomas are more commonly seen in adults. Currently, the primary treatment for ependymoma involves surgery to remove as much of the tumor as safely possible, followed by radiation therapy.

The role of chemotherapy in treating ependymoma remains a topic of debate, and it is being investigated in ongoing clinical trials. While there are currently no approved targeted therapies for ependymoma, research efforts are focused on identifying new molecular targets. As a result, survival rates have seen modest improvement of 80% in the last decade, with survivors suffering from the debilitating side effects of treatment-related surgery and radiation.

Traditionally, histopathology, or the microscopic examination of tissue samples, has been used to diagnose and assess the risk associated with ependymoma. However, this approach has not been reliable in predicting patient survival, except for certain WHO Grade I tumors like subependymomas. The inconsistency in histopathologic grading has driven researchers and clinicians to explore more sensitive and unbiased molecular approaches to identify reliable prognostic markers and understand the molecular biology of ependymoma, with the goal of developing targeted therapies.

Decoding Ependymoma: A Molecular Revolution

Molecular Ependymoma Illustration

Thanks to advanced technologies in transcriptomics, genomics, and epigenomics (collectively known as '-omics'), we are now gaining unprecedented insights into ependymoma. These approaches have revealed that ependymomas are not a single entity but rather a collection of distinct subgroups, each with unique clinical and biological characteristics. The most comprehensive analysis to date has identified at least nine molecular subgroups.

Supratentorial (ST) ependymomas are divided into subtypes based on gene fusions, with C11ORF95-RELA fusions being the most common. YES-associated protein 1 (YAP1) oncogene fusions with other gene partners define additional subgroups, ST-EPN-RELA and ST-EPN-YAP1. Posterior fossa (PF) ependymomas are classified into PF-EPN-A tumors, which are associated with poorer outcomes and relatively balanced genomes, and PF-EPN-B tumors, characterized by increased genomic instability and more favorable outcomes. Grade I subependymomas exist within both ST and PF compartments. Spinal ependymomas often have NF2 mutations or deletions, and include subependymoma and myxopapillary ependymoma variants. These detailed '-omics' studies emphasize that ependymomas are a diverse group of diseases, each requiring a tailored approach.

  • Histopathologic grading of Grade II or III EPN outside of clinical trials should not be used to risk stratify future patients.
  • Ependymoma is composed of at least nine different diseases.
  • Frequent gene fusions define supratentorial ependymoma, namely, C11ORF95-RELA.
  • '-omics'-based tumor characterization will continue to unravel the molecular basis of ependymoma and its subgroups.
Molecular profiling, using Illumina DNA methylation analysis, has allowed researchers to assess the impact of molecular subgroups and clinical variables. For instance, a study of four distinct PF EPN cohorts indicated that while radiotherapy is effective for gross-totally resected PF-EPN-A tumors, it has limited benefit in patients with subtotal resections. Ongoing clinical trials addressing other treatment modalities, such as chemotherapy (ACNS0831), need to consider molecular subgroup context in case of PF-EPN-B.

The Future of Ependymoma Research

The '-omics'-based approaches have been instrumental in identifying the primary drivers of ependymoma. Additional applications, such as epigenomics, proteomics, single-cell analysis, and metabolomics, may reveal other oncogenic drivers and offer further insights into the mechanisms of EPN-genesis. Advanced genomic sequencing might also uncover lesions or mutations that have been previously missed. By continuing partnerships between researchers and clinicians, and working toward international collaboration and shared access to samples, models, and data.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

1

How has the understanding of ependymoma changed with the advent of molecular biology?

Ependymomas are no longer viewed as a single disease but rather as a collection of at least nine distinct molecular subgroups. These subgroups include supratentorial ependymomas like ST-EPN-RELA (defined by C11ORF95-RELA fusions) and ST-EPN-YAP1 (defined by YAP1 fusions), posterior fossa ependymomas such as PF-EPN-A (associated with poorer outcomes) and PF-EPN-B (characterized by genomic instability), and spinal ependymomas often linked to NF2 mutations. Recognizing these distinct subgroups is crucial for tailoring treatments and improving patient outcomes.

2

Why is traditional histopathology insufficient for assessing and predicting the prognosis of ependymoma?

Traditional histopathology, which involves microscopic examination of tissue samples, has limitations in accurately predicting patient survival in ependymoma cases, except for WHO Grade I tumors like subependymomas. This inconsistency has led researchers to explore molecular approaches like transcriptomics, genomics, and epigenomics ('-omics') to identify more reliable prognostic markers. These '-omics' technologies offer deeper insights into the molecular biology of ependymoma, enabling the development of targeted therapies based on specific molecular characteristics rather than broad histological classifications.

3

What role do '-omics' approaches play in advancing our understanding and treatment of ependymoma?

The '-omics'-based approaches, including transcriptomics, genomics, and epigenomics, have played a crucial role in identifying the primary drivers of ependymoma. These technologies enable comprehensive molecular profiling, which helps in classifying ependymomas into distinct subgroups based on their genetic and epigenetic characteristics. These approaches offer insights into potential oncogenic drivers and mechanisms of EPN-genesis, paving the way for the development of targeted therapies tailored to specific molecular profiles.

4

What are the current treatment options for ependymoma, and what is the focus of ongoing research?

Current treatment for ependymoma primarily involves surgery to remove as much of the tumor as possible, followed by radiation therapy. The role of chemotherapy is still under investigation. However, there are currently no approved targeted therapies specifically for ependymoma. Research is focused on identifying new molecular targets using '-omics' technologies to develop more effective and personalized treatments. Clinical trials, like ACNS0831, are incorporating molecular subgroup context, particularly for PF-EPN-B tumors, to assess the efficacy of different treatment modalities.

5

What are the long-term implications for ependymoma survivors, and how is research addressing these challenges?

While survival rates for ependymoma have modestly improved to around 80% in the last decade, survivors often suffer from debilitating side effects related to surgery and radiation therapy. Current research is aimed at identifying new molecular targets through advanced genomic sequencing and '-omics' studies to develop targeted therapies. These therapies aim to reduce reliance on traditional treatments like surgery and radiation, potentially minimizing long-term side effects and improving the quality of life for ependymoma survivors. Collaboration and shared access to samples and data are crucial for advancing this research.

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