From the Guidelines
Ependymomas are characterized by distinct genetic profiles based on their location, with supratentorial ependymomas frequently displaying RELA or YAP1 gene fusions, and posterior fossa ependymomas divided into Group A and Group B, each with its own prognosis and treatment approach. The genetic factors contributing to the development and behavior of ependymomas are complex and varied, involving multiple molecular subgroups with distinct DNA methylation profiles and associated genetic alterations 1. These genetic factors are crucial for diagnosis, prognosis, and treatment planning, as they can influence the tumor's behavior and response to treatment. For example, supratentorial ependymomas with RELA fusions are associated with more aggressive behavior, while those with YAP1 fusions have a more favorable prognosis 1.
Some key genetic alterations in ependymomas include:
- RELA or YAP1 gene fusions in supratentorial ependymomas
- NF2 gene mutations or deletions in spinal ependymomas, particularly in myxopapillary variants
- CDKN2A deletions, chromosome 1q gain, and mutations in chromatin remodeling genes like ARID1A and ARID1B
- H3K27me3 loss in Group A posterior fossa ependymomas, which is associated with poor prognosis 1
Understanding these genetic factors is essential for developing targeted therapies and improving treatment outcomes for patients with ependymomas. The identification of specific genetic alterations can help guide treatment decisions, such as the use of more aggressive treatment approaches for Group A posterior fossa ependymomas. Further research is needed to fully elucidate the genetic landscape of ependymomas and to develop effective targeted therapies for these tumors 1.
From the Research
Genetic Factors of Ependymoma
The genetic factors of ependymoma, a type of brain tumor, are complex and involve various molecular mechanisms. Some of the key genetic factors include:
- Overexpression of chemoresistance and DNA repair-related proteins, such as RRM1, ERCC1, TOPO1, and class III β-tublin (TUBB3) 2
- High expression rates of transporter proteins that mediate multi-drug resistance, including BCRP and MRP1 2
- Increased expression of DNA synthesis enzymes, such as TS, in cranial ependymomas compared to spinal lesions 2
- Elevated expression of TOP2A and TUBB3 in high-grade lesions 2
- Epigenetic alterations, such as transcriptional programs activated by oncofusion proteins and alterations in histone modifications, play an important role in the development of ependymoma 3
- Cyclin D1 overexpression is associated with progression and radio-resistance of pediatric ependymomas 4
- Genetic aberrations, such as large genomic regions, make it difficult to differentiate between passenger and driver genes 5
- Distinct molecular and genetic differences in tumorigenesis between different subgroups of ependymomas, including posterior fossa, supratentorial, and pediatric tumors 6
Molecular Mechanisms
The molecular mechanisms underlying ependymoma involve:
- DNA repair and synthesis enzymes, such as RAD51 and CCND1, which are up-regulated in supratentorial and infratentorial ependymomas 4
- Homologous recombination activities of DNA repair, which are decreased in CCND1-deficient cells 4
- Epigenetic alterations, which interact with developmental epigenetic programs in the cell of origin to initiate neoplastic transformation and disease progression 3
Subgroups of Ependymoma
Different subgroups of ependymoma have distinct genetic and molecular characteristics, including:
- Posterior fossa ependymomas, which have a balanced karyotype in a significant subset of cases 5
- Supratentorial ependymomas, which have increased expression of TS and other DNA synthesis enzymes 2
- Pediatric ependymomas, which have distinct molecular and genetic differences in tumorigenesis compared to adult ependymomas 3, 6