Understanding epilepsy in pediatric tumors

September 20, 2018, The Korea Advanced Institute of Science and Technology (KAIST)
Understanding epilepsy in pediatric tumors
Preoperative and postoperative brain MRI (left panel), tumor H&E (right upper panel) and GFAP immunohistochemical (right lower panel) staining images from a patient with ganglioglioma (GG231) carrying the BRAFV600E mutation. The white arrow and the black arrowhead indicate the brain tumor and a dysplastic neuron, respectively. Credit: KAIST

Pediatric brain tumors are characterized by frequent complications due to intractable epilepsy compared to adult brain tumors. However, the genetic cause of refractory epilepsy in pediatric brain cancer has not been elucidated yet, and it is difficult to treat patients because the tumors do not respond to existing antiepileptic drugs and interfere with children's development.

A Korean research team led by Professor Jeong Ho Lee of the Graduate School of Medical Science and Engineering at the Korea Advanced Institute of Science and Technology (KAIST) has recently identified a neuronal BRAF somatic mutation that causes intrinsic epileptogenicity in pediatric brain tumors. Their research results were published online in Nature Medicine on September 17.

The research team studied patients' tissue diagnosed with ganglioglioma (GG), one of the main causes of tumor-associated , and found that the BRAF V600E somatic mutation is involved in the development of by using deep DNA sequencing. This mutation was carried out in an animal model to reproduce the pathology of GG and to observe seizures to establish an animal model for the treatment of epileptic seizures caused by .

Using immunohistochemical and transcriptome analysis, they realized that the BRAF V600E mutation that arose in early progenitor cells during embryonic brain formation led to the acquisition of intrinsic epileptogenic properties in neuronal lineage cells, whereas tumorigenic properties were attributed to a high proliferation of glial lineage cells exhibiting the mutation. Notably, researchers found that seizures in mice were significantly alleviated by intraventricular infusion of the BRAF V600E inhibitor, Vemurafenib, a clinical anticancer drug.

The authors said, "Our study offers the first direct evidence that the BRAF somatic mutation arising from neural stem cells plays a key role in epileptogenesis in the tumor. This study also showed a new therapeutic target for -associated epileptic disorders."

Explore further: V600E BRAF mutation tied to worse survival in CRC liver mets

More information: Hyun Yong Koh et al, BRAF somatic mutation contributes to intrinsic epileptogenicity in pediatric brain tumors, Nature Medicine (2018). DOI: 10.1038/s41591-018-0172-x

Related Stories

V600E BRAF mutation tied to worse survival in CRC liver mets

May 21, 2018
(HealthDay)—For patients undergoing resection of colorectal liver metastases (CRLM), the presence of the V600E BRAF mutation is associated with worse prognosis, according to a study published online May 16 in JAMA Surgery.

A breakthrough for understanding glioblastoma—origin cells for deadly brain tumors identified

August 2, 2018
A new study by KAIST researchers identified where the mutation causing glioblastoma starts. According to the study, neural stem cells away from the tumor mass are the cells of origin that contain mutation drivers for glioblastoma, ...

Uncommon BRAF mutation in melanoma sensitive to MEK inhibitor drug therapy

July 16, 2012
An uncommon mutation of the BRAF gene in melanoma patients has been found to respond to MEK inhibitor drugs, providing a rationale for routine screening and therapy in melanoma patients who harbor the BRAF L597 mutation.

Study finds targetable mutation in rare brain tumor

January 12, 2014
A team led by investigators from Massachusetts General Hospital (MGH), Brigham and Women's Hospital (BWH) and the Broad Institute has found that a gene mutation associated with several types of cancer also may be responsible ...

Mechanism leading to cortical malformation from brain-only mutations identified

July 3, 2018
Focal malformations of cortical development (FMCDs) are a heterogeneous group of brain cortical abnormalities. These conditions are the most common causes of refractory epilepsy in children and are highly associated with ...

Mutations taking place only in the brain identified as the cause of intractable epilepsy

March 24, 2015
Epilepsy is a brain disorder that afflicts more than 50 million people worldwide. Many epilepsy patients can control their symptoms through medication, but about 30% suffer from intractable epilepsy and are unable to manage ...

Recommended for you

Mutant cells colonize our tissues over our lifetime

October 18, 2018
By the time we reach middle age, more than half of the oesophagus in healthy people has been taken over by cells carrying mutations in cancer genes, scientists have uncovered. By studying normal oesophagus tissue, scientists ...

Breastfeeding protects infants from antibiotic-resistant bacteria

October 18, 2018
A recent study completed at the University of Helsinki investigated the amount and quality of antibiotic-resistant bacteria in breast milk and gut of mother-infant pairs. The findings have been published in the journal Nature ...

Study involving hundreds of patient samples may reveal new treatment options of leukemia

October 17, 2018
After more than five years and 672 patient samples, an OHSU research team has published the largest cancer dataset of its kind for a form of leukemia. The study, "Functional Genomic Landscape of Acute Myeloid Leukemia", published ...

A 150-year-old drug might improve radiation therapy for cancer

October 17, 2018
A drug first identified 150 years ago and used as a smooth-muscle relaxant might make tumors more sensitive to radiation therapy, according to a recent study led by researchers at The Ohio State University Comprehensive Cancer ...

Loss of protein p53 helps cancer cells multiply in 'unfavourable' conditions

October 17, 2018
Researchers have discovered a novel consequence of loss of the tumour protein p53 that promotes cancer development, according to new findings in eLife.

New method uses just a drop of blood to monitor lung cancer treatment

October 17, 2018
Dr. Tasuku Honjo won the 2018 Nobel Prize in physiology or medicine for discovering the immune T-cell protein PD-1. This discovery led to a set of anti-cancer medications called checkpoint inhibitors, one of the first of ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.