Tuberous sclerosis complex (TSC) is a multisystem, autosomal dominant disorder with a wide clinical spectrum. The most common brain tumor associated with TSC is the low grade subependymal giant cell astrocytoma. Reports of high grade primary brain tumors in patients with TSC are rare. TSC1/2 mutation has been identified in glioblastoma (GBM) even though it probably does not increase the overall risk for GBM in patients with TSC. We present a 58-year-old patient with known TSC, admitted for new neurological symptoms, diagnosed with a large heterogeneous tumor involving most of the corpus callosum. Stereotactic needle brain biopsy confirmed the diagnosis to be GBM. Five previously reported similar cases are reviewed, reflecting diversity in clinical and radiological findings and indicating that a high index of clinical suspicion must be maintained in patients with TSC.

Glial fibrillary acidic protein (GFAP) is an intermediate filament that provides mechanical support to astrocytes. Rs2070935 is a single nucleotide polymorphism (SNP) located in the promoter region of the GFAP gene. The aim of this pilot study is to investigate GFAP expression at mRNA, protein levels and rs2070935 polymorphism in 50 different grade human astrocytoma samples. GFAP expression at mRNA level was measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR) with SYBR Green dye, whereas the translational activity of the following gene was detected using western blot assay. Furthermore, genotypes of rs2070935 were identified using qPCR with TaqMan probes. As a result, GFAP mRNA and protein expression was found to be declining with increasing astrocytoma grade (p < 0.05). A tendency was observed between increased GFAP mRNA expression and shorter grade IV astrocytoma patient survival (p = 0.2117). The rs2070935 CC genotype was found to be associated with increased GFAP translational activity in grade II astrocytoma (p = 0.0238). Possible links between rs2070935 genotypes and alternative splicing of GFAP were also observed. The rs2070935 AA genotype was found to be associated with poor clinical outcome for grade IV astrocytoma patients (p = 0.0007), although the following data should be checked in a larger sample size of astrocytoma patients.

KIAA1549-BRAF is the most frequently identified genetic mutation in sporadic pilocytic astrocytoma (PA), creating a fusion BRAF (f-BRAF) protein with increased BRAF activity. Fusion-BRAF-expressing neural stem cells (NSCs) exhibit increased cell growth and can generate glioma-like lesions following injection into the cerebella of naïve mice. Increased Iba1+ monocyte (microglia) infiltration is associated with murine f-BRAF-expressing NSC-induced glioma-like lesion formation, suggesting that f-BRAF-expressing NSCs attract microglia to establish a microenvironment supportive of tumorigenesis. Herein, we identify Ccl2 as the chemokine produced by f-BRAF-expressing NSCs, which is critical for creating a permissive stroma for gliomagenesis. In addition, f-BRAF regulation of Ccl2 production operates in an ERK- and NFκB-dependent manner in cerebellar NSCs. Finally, Ccr2-mediated microglia recruitment is required for glioma-like lesion formation in vivo, as tumor do not form in Ccr2-deficient mice following f-BRAF-expressing NSC injection. Collectively, these results demonstrate that f-BRAF expression creates a supportive tumor microenvironment through NFκB-mediated Ccl2 production and microglia recruitment.

Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyze the transfer of methyl groups from S-adenosyl-l-methionine to nitrogen atoms on arginine residues. Arginine methylation is involved in multiple biological processes, such as signal transduction, mRNA splicing, transcriptional control, DNA repair, and protein translocation. Currently, 10 patients have been described with mutations in PRMT7. The shared findings include: hypotonia, intellectual disability, short stature, brachydactyly, and mild dysmorphic features. We describe the prenatal, postnatal, and pathological findings in two male sibs homozygote for a mutation in PRMT7. Both had intrauterine growth restriction involving mainly the long bones. In addition, eye tumor was found in the first patient, and nonspecific brain calcifications and a systemic venous anomaly in the second. The pregnancy of the first child was terminated and we describe the autopsy findings. The second child had postnatal growth restriction of prenatal onset, hypotonia, strabismus, sensorineural hearing loss, genitourinary and skeletal involvement, and global developmental delay. He had dysmorphic features that included frontal bossing, upslanting palpebral fissures, small nose with depressed nasal bridge, and pectus excavatum. Our patients provide additional clinical and pathological data and expand the phenotypic manifestations associated with PRMT7 homozygote/compound heterozygote mutations to include brain calcifications and delayed myelination, and congenital orbital tumor.