Exploring the Possible Role of Mutations in MTOR pathway Genes in the Pathogenesis of DNET tumors

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Anna Maria Buccoliero

Meyer Children's Hospital
Florence, Italy

CBTN Samples Used


CBTN Participants


CBTN Samples


Institutional Funds

About this


Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNET) are the most frequently identified tumors in epilepsy surgical series, yet their molecular determinants are poorly understood. Their characteristic histopathological features, together with the coexistence with cortical dysplasia, their focal nature, and the expression of stem cell markers (such as CD34), suggest a developmental origin of these lesions. BRAF-V600E and FGFR1 mutations are commonly identified in ganglioglioma/DNETs, although the reported frequencies vary significantly across surgical series. A recent study identified a novel FGFR2-INA fusion gene in two cases of unclassified, GG or DNET, glioneuronal tumors. This data has not been replicated yet, further studies are needed to elucidate if this rearrangement is a common feature of one of these low-grade epileptogenic tumors.

Recent studies have proposed over-activation of the mTOR pathway as a possible cause of DNET. Previous studies had demonstrated activating mutations in genes belonging to the mTOR signalling pathway in lesions associated with intractable epilepsy, such as FCD and hemimegalencephaly. However, there are very few similar studies in DNETs. It appears that enhanced mTOR signalling is central to the pathogenesis of intractable epilepsy-associated lesions, whether tumoral or non-tumoral. Comprehensive studies on the genetic basis of this hyperactivation have not been performed until now in DNET samples.

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What are the goals of this project?

The goals of this project are to test the possible role of mutations in genes belonging to the MTOR pathway in the pathogenesis of DNET and to explore whether mutations in MTOR pathway genes coexists with alterations in BRAF or FGFR1 in DNETs.

What is the impact of this project?

Finding mutations in mTOR pathway genes in DNETs could increase knowledge on the pathogenesis of such tumors and eventually pave the way for targeted therapies, based, for example, on mTOR inhibitors, which may be most relevant for patients whose tumors are incompletely resected and for those with residual seizures after surgery.

Why the CBTN request is important to this project?

The access to the CBTN samples will allow to investigate the role of DNA mutations in the mTOR pathway genes in the pathogenesis of DNET tumors and to clarify their possible connection with BRAF or FGFR1 alterations. Since our approach is addressed towards deep characterization of a restricted number of genes, by accessing to CBTN biobank we will also be able to integrate our results with those already generated by WGS and annotated in the Pedcbio portal.

Specimen Data

The Children's Brain Tumor Network contributed to this project by providing DNA and RNA samples.