• Low-grade glioma
• Neurodeficit
• Second-look surgery

• Humans
• Glioma/surgery
• Brain Neoplasms/surgery
• Child
• Second-Look Surgery/methods
• Retrospective Studies
• Neurosurgical Procedures/methods

• 1p/19q-codeleted
• Astrocytoma
• Chemotherapy
• Gliomas
• Isocitrate dehydrogenase type mutant
• Oligodendroglioma
• Pediatric gliomas
• Radiotherapy

• CDC42BPA (MRCK) gene alteration
• MAPK pathway activation and inhibition
• desmoplastic infantile astrocytoma
• novel CDC42BPA::BRAF fusion

• National Cancer Institute
• National Institutes of Health

• Drug resistant epilepsy
• Epilepsy surgery
• Glioneuronal tumor
• Low grade epilepsy associated tumor
• Neuronal tumor

• Humans
• Adult
• Brain Neoplasms/diagnostic imaging
• Brain Neoplasms/therapy
• Brain Neoplasms/genetics
• Epilepsy/diagnosis
• Epilepsy/etiology
• Epilepsy/therapy
• Neoplasms, Neuroepithelial/complications
• Neoplasms, Neuroepithelial/pathology
• Neoplasms, Neuroepithelial/surgery
• Neuroglia/pathology
• Neurons/pathology

• BRAF
• Brain tumors
• Case report
• Neurosurgery
• Vemurafenib

• Chemotherapy
• Low grade glioma
• Pediatric brain tumor
• Target therapy

• MAPK signaling pathway
• RAF
• VP0 cleavage
• enterovirus
• genome replication
• vemurafenib
• virus assembly

• CID-HKU1-11, ZDKJ202003 etc. the Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region, etc

Desmoplastic infantile astrocytoma (DIA) is rare, cystic and solid tumor of infants usually found in superficial cerebral hemispheres. Although DIA is usually benign, uncommon cases bearing malignant histological and aggressive clinical features have been described in the literature. We report a newborn patient who was diagnosed with a DIA and died postresection. Pathologic examination revealed that the main part of the tumor had benign features, but the internal region showed areas with a more aggressive appearance, with higher-proliferative cells, anaplastic GFAP positive cells with cellular polymorphism, necrosis foci, vascular hyperplasia with endothelial proliferation and microtrombosis. Genetic study, performed in both regions of the tumor, showed a BRAF V600E mutation and a homozygous deletion in PTEN, without changes in other relevant genes like EGFR, CDKN2A, TP53, NFKBIA, CDK4, MDM2 and PDGFRA. Although PTEN homozygous deletions are described in gliomas, the present case constitutes the first report of a PTEN mutation in a DIA, and this genetic feature may be related to the malignant behavior of a usually benign tumor. These genetic findings may point at the need of further and deeper genetic characterization of DIAs, in order to better understand the biology of this tumor and to obtain new prognostic approaches, a better clinical management and targeted therapies, especially in malignant cases of DIA.

• Atypical
• BRAF V600E
• Desmoplastic infantile astrocytoma
• PTEN

• BBSFOP
• children
• high grade glioma
• infant
• young

• Brain Neoplasms/genetics
• Brain Neoplasms/therapy
• Child, Preschool
• Glioma/genetics
• Glioma/therapy
• Humans
• Infant

• 23536 Cancer Research UK

Background: Although low-grade glioma (LGG) has a good prognosis, it is prone to malignant transformation into high-grade glioma. It has been confirmed that the characteristics of inflammatory factors and immune microenvironment are closely related to the occurrence and development of tumors. It is necessary to clarify the role of inflammatory genes and immune infiltration in LGG.

Methods: We downloaded the transcriptome gene expression data and corresponding clinical data of LGG patients from the TCGA and GTEX databases to screen prognosis-related differentially expressed inflammatory genes with the difference analysis and single-factor Cox regression analysis. The prognostic risk model was constructed by LASSO Cox regression analysis, which enables us to compare the overall survival rate of high- and low-risk groups in the model by Kaplan–Meier analysis and subsequently draw the risk curve and survival status diagram. We analyzed the accuracy of the prediction model via ROC curves and performed GSEA enrichment analysis. The ssGSEA algorithm was used to calculate the score of immune cell infiltration and the activity of immune-related pathways. The CellMiner database was used to study drug sensitivity.

Results: In this study, 3 genes (CALCRL, MMP14, and SELL) were selected from 9 prognosis-related differential inflammation genes through LASSO Cox regression analysis to construct a prognostic risk model. Further analysis showed that the risk score was negatively correlated with the prognosis, and the ROC curve showed that the accuracy of the model was better. The age, grade, and risk score can be used as independent prognostic factors (p < 0.001). GSEA analysis confirmed that 6 immune-related pathways were enriched in the high-risk group. We found that the degree of infiltration of 12 immune cell subpopulations and the scores of 13 immune functions and pathways in the high-risk group were significantly increased by applying the ssGSEA method (p < 0.05). Finally, we explored the relationship between the genes in the model and the susceptibility of drugs.

Conclusion: This study analyzed the correlation between the inflammation-related risk model and the immune microenvironment. It is expected to provide a reference for the screening of LGG prognostic markers and the evaluation of immune response.

• drug sensitivity
• immune infiltration
• inflammatory response
• low-grade glioma
• prognosis

A hallmark of pediatric low-grade glioma (pLGG) is aberrant signaling of the mitogen activated protein kinase (MAPK) pathway. Hence, inhibition of MAPK signaling using small molecule inhibitors such as MEK inhibitors (MEKi) may be a promising strategy.

In this multi-center retrospective centrally reviewed study, we analyzed 18 patients treated with the MEKi trametinib for progressive pLGG as an individual treatment decision between 2015 and 2019. We have investigated radiological response as per central radiology review, molecular classification and investigator observed toxicity.

We observed 6 partial responses (PR), 2 minor responses (MR), and 10 stable diseases (SD) as best overall responses. Disease control rate (DCR) was 100% under therapy. Responses were observed in KIAA1549:BRAF- as well as neurofibromatosis type 1 (NF1)-driven tumors. Median treatment time was 12.5 months (range: 2 to 27 months). Progressive disease was observed in three patients after cessation of trametinib treatment within a median time of 3 (2–4) months. Therapy related adverse events occurred in 16/18 patients (89%). Eight of 18 patients (44%) experienced severe adverse events (CTCAE III and/or IV; most commonly skin rash and paronychia) requiring dose reduction in 6/18 patients (33%), and discontinuation of treatment in 2/18 patients (11%).

Trametinib was an active and feasible treatment for progressive pLGG leading to disease control in all patients. However, treatment related toxicity interfered with treatment in individual patients, and disease control after MEKi withdrawal was not sustained in a fraction of patients. Our data support in-class efficacy of MEKi in pLGGs and necessity for upfront randomized testing of trametinib against current standard chemotherapy regimens.

• BRAF
• MAPK pathway
• MEK inhibitor
• NF1
• Pediatric low-grade glioma
• Targeted therapy
• Trametinib

• Gene Fusion/genetics
• Glioma/genetics
• Humans
• Infant
• Neoplasm Grading
• Prognosis
• Treatment Outcome

• A23536 Cancer Research UK
• G0701018 Medical Research Council
• G1100578 Medical Research Council
• MR/N004272/1 Medical Research Council
• 23536 Cancer Research UK
• 27725 Cancer Research UK
• P30 CA008748 NCI NIH HHS
• P30 CA021765 NCI NIH HHS
• P01 CA096832 NCI NIH HHS

• Automated real-time PCR
• BRAF
• low grade glioma
• molecular diagnosis

• Cell Cycle
• Epigenesis, Genetic
• Europe
• Gene Expression Regulation, Neoplastic
• Genetic Predisposition to Disease
• Genomics
• Humans
• Immune System
• Mutation
• Neoplasms/genetics
• Neoplasms/therapy
• Pediatrics/methods
• Signal Transduction
• Tumor Microenvironment
• United States

Alterations of the v-raf murine sarcoma viral oncogene homolog B (BRAF) have been extensively studied in several tumor entities and are known to drive cell growth in several tumor entities. Effective targeted therapies with mutation-specific small molecule inhibitors have been developed and established for metastasized malignant melanoma. The BRAF V600E mutation and KIAA1549-BRAF fusion are alterations found in several brain tumors and show a distinct prognostic impact in some entities. Besides the diagnostic significance for the classification of central nervous system tumors, these alterations present possible therapy targets that may be exploitable for oncological treatments, as it has been established for malignant melanomas. In this review the different central nervous system tumors harboring BRAF alterations are presented and the diagnostic significance, prognostic role, and therapeutic potential are discussed.

• BRAF V600E
• KIAA1549-BRAF
• MAPK
• astrocytoma
• glioblastoma

• pediatric low-grade glioma
• braf
• targeted therapy
• radiation therapy