Low-grade developmental and epilepsy associated brain tumors: a critical update 2020

Abstract

Brain tumors represent the second most frequent etiology in patients with focal seizure onset before 18 years of age and submitted to epilepsy surgery. Hence, this category of brain tumors, herein defined as low-grade, developmental, epilepsy-associated brain tumors (LEAT) is different from those frequently encountered in adults as (A): 77% of LEAT occur in the temporal lobe; (B): the vast majority of LEAT are of low malignancy and classified as WHO I°; (C): LEAT are often composed of mixed glial and neuronal cell components and present with variable growth patterns including small cysts or nodules; (D): LEAT do not share common gene driving mutations, such as IDH1 or 1p/19q co-deletions. Characteristic entities comprise the ganglioglioma (GG), the dysembryoplastic neuroepithelial tumor (DNT), the angiocentric glioma (AG), the isomorphic diffuse glioma (IDG) and the papillary glio-neuronal tumor (PGNT), representing 73.2% of 1680 tumors collected in a large German series of 6747 patients submitted to epilepsy surgery. In the realm of exciting discoveries of genetic drivers of brain tumors new genes have been also reported for LEAT. BRAF V600E mutations were linked to GG with CD34 expression, FGFR1 mutations to DNT, MYB alterations to AG and also IDG and PRKCA fusions to PGNT, suggesting the possibility to also develop a genetically driven tumor classification scheme for LEAT. Rare availability of LEAT in a single center is a challenging obstacle, however, to systematically unravel the neurobiological nature and clinical behavior of LEAT. Other challenges in need of clarification include malignant tumor progression of LEAT entities, seizure relapse in patients following bulk tumor resection and the controversial issue of associated focal cortical dysplasia as additional pathomechanism. In order to advance our understanding and promote reliable diagnostic work-up of LEAT, we recommend, therefore, international collaboration to achieve our goals.

RETRACTED ARTICLE: MYC-mediated upregulation of PNO1 promotes glioma tumorigenesis by activating THBS1/FAK/Akt signaling

“…5A). Many intersection DEGs, including CCND1, RAC1, PRKCA, THBS1, and AKT3, have been reported to involve in glioma tumorigenesis [18][19][20][21][22][23] and were further confirmed by RT-PCR in U251-shPNO1 cells (Fig. 5B).…”

Radiohistogenomics of pediatric low-grade neuroepithelial tumors

“…GGs typically arise from cortical/juxtacortical regions. GG is the most common tumor in the LEAT family [82]. It predominantly occurs in children and young adults and characteristically present with temporal lobe epilepsy.…”

“…DNT is another cortical/juxtacortical tumor in the LEAT family that typically involves the temporal lobe, with preferential involvement of the mesial temporal lobe, and typically presents with temporal lobe epilepsy [82].…”

“…PGNT is a rare glioneuronal tumor that occurs in the supratentorial compartment and is in the LEAT family [82]. Smaller PGNTs are primarily within the gray matter, but larger tumors extend into the white matter [111,112].…”

Identification and Verification on Prognostic Index of Lower-Grade Glioma Immune-Related LncRNAs

“…Glioma is the most common type of primary tumors in the nervous system (1,2). Previous studies have shown that the immune infiltration microenvironment of lower-grade glioma (LGG) was strongly linked with the prognosis of patients (3).…”