J Korean Neurosurg Soc.  2019 May;62(3):313-320. 10.3340/jkns.2019.0033.

Clinical Pearls and Advances in Molecular Researches of Epilepsy-Associated Tumors

• Phi JH
• Kim SK

• KMID: 2453236
• DOI: http://doi.org/10.3340/jkns.2019.0033

Abstract

Brain tumors are the second most common type of structural brain lesion that causes chronic epilepsy. Patients with low-grade brain tumors often experience chronic drug-resistant epilepsy starting in childhood, which led to the concept of long-term epilepsy-associated tumors (LEATs). Dysembryoplastic neuroepithelial tumor and ganglioglioma are representative LEATs and are characterized by young age of onset, frequent temporal lobe location, benign tumor biology, and chronic epilepsy. Although highly relevant in clinical epileptology, the concept of LEATs has been criticized in the neuro-oncology field. Recent genomic and molecular studies have challenged traditional views on LEATs and low-grade gliomas. Molecular studies have revealed that low-grade gliomas can largely be divided into three groups : LEATs, pediatric-type diffuse low-grade glioma (DLGG; astrocytoma and oligodendroglioma), and adult-type DLGG. There is substantial overlap between conventional LEATs and pediatric-type DLGG in regard to clinical features, histology, and molecular characteristics. LEATs and pediatric-type DLGG are characterized by mutations in BRAF, FGFR1, and MYB/MYBL1, which converge on the RAS-RAF-MAPK pathway. Gene (mutation)-centered classification of epilepsy-associated tumors could provide new insight into these heterogeneous and diverse neoplasms and may lead to novel molecular targeted therapies for epilepsy in the near future.

Keyword

Brain neoplasms; Seizures; Epilepsy; Glioma; Classification

MeSH Terms

Age of Onset
Astrocytoma
Biology
Brain
Brain Neoplasms
Classification
Epilepsy
Ganglioglioma
Glioma
Humans
Molecular Targeted Therapy
Neoplasms, Neuroepithelial
Seizures
Temporal Lobe

Figure

• 

  Fig. 1. Molecular genetic pathways in long-term epilepsy-associated tumors (LEATs) and pediatric type diffuse low-grade glioma (DLGG). Two major signaling pathways, the RAS-RAF-MAPK (green) and PI3K-AKT-mTOR (blue) play major role in LEATs. Upstream in receptor signaling, FGFR1 mutations have been described in dysembryoplastic neuroepithelial tumors. Activation of RAS-RAF-MAPK pathway by BRAF V600E mutation is frequently detected in gangliogliomas. BRAF and MEK1/2 are pharmacological targets for therapy (pink). MAPK activation is regulated by substrates of the PI3K–AKT–mTOR signaling cascade (red links). c-MYB/MYBL1 (purple) is altered in angiocentric gliomas. Genetic alterations described in LEATs are designated by a lightning bolt. Reprint from Blümcke et al. [4] with permission from Springer Nature.

Reference

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