Angiocentric glioma-associated seizures: The possible role of EATT2, pyruvate carboxylase and glutamine synthetase

Purpose: Our purpose was to better understand the pathogenesis of seizures associated with angiocentric glioma. Angiocentric glioma is an indolent and rare low-grade glioma. Its typical clinical presentation is with epileptic seizures. The pathogenesis of tumor-associated seizures is poorly understood. Among the possible pathomechanisms, the increased neurotoxic concentrations of the glutamate has been proposed. Glutamate transporters, pyruvate carboxylase and glutamine synthetase are involved in maintaining the physiological concentration of glutamate in the inter synaptic spaces. Methods: We evaluated the immunohistochemical expression of EAAT2 (the most important glutamate transporter), pyruvate carboxylase and glutamine synthetase in 17 angiocentric gliomas. Results: EAAT2 was never expressed (0%) in the neoplastic cells in none of the cases studied. Pyruvate carboxylase was expressed in the cytoplasm of the neoplastic cells in 16/17 cases (94 %). Glutamine synthetase was expressed in the cytoplasm of the neoplastic cells in 15/17 cases (88 %). Conclusion: The net result of this enzymatic expression, in particular considering the loss of EAAT2, could be an increased glutamate concentration in the synaptic clef, which might increase local network excitability initially involving intratumoral neurons. The observation that the angiocentric glioma-associated epilepsy might be at least in part related to EAAT2 deficiency opens up interesting therapeutic perspectives

Mn magnetism in icosahedral quasicrystalline Al72.4Pd20.5Mn7.1

The unusual magnetism of manganese atoms in an icosahedral Al72.4Pd20.5Mn7.1 single-grain quasicrystal was studied by Al-27 nuclear magnetic resonance (NMR), magnetic susceptibility, and electrical resistivity measurements. Between room temperature and 50 K both the Al-27 NMR linewidth and the frequency shift exhibit a Curie-Weiss-type, 1/(T-theta) temperature dependence. At lower temperatures a significant narrowing of the linewidth, concomitant with a reduction of the frequency shift is observed. These features can be explained by a gradual reduction of the local exchange magnetic field at the position of the Al-27 nuclei that is transferred from the manganese d moments via the conduction electrons. Two possible origins of this phenomenon are discussed: (i) the Kondo-like screening of manganese moments by the conduction electrons and (ii) the ''resistivity'' -damping of the RKKY interaction due to increasing electron localization at low temperatures

Low-temperature thermal conductivity of a single-grain Y-Mg-Zn icosahedral quasicrystal

We report measurements of the thermal conductivity kappa(T) of a single-grain icosahedral Y8.6Me34.6Zn56.8 in the temperature range between 0.1 and 300 K. The quasilattice thermal conductivity kappa(ph) increases monotonically with T by three orders of magnitude between 0.1 and 23 K. Above 23 K, kappa(ph)(T) decreases substantially with increasing temperature, typical for high-quality single grain quasicrystals. The decrease ends in a minimum at approximately 140 K. The interpretation of our data is based on a Debye-type relaxation time approximation. At very low temperatures, the corresponding fit reveals that the phonon mean free path is of the order of the smallest sample dimension, while at high temperatures, a power-law decrease of the phonon scattering time with increasing temperature evidences the effect of structural scattering on the mean free path of itinerant quasilattice excitations. The behavior of kappa(ph)(T) at intermediate temperatures may best be fit by assuming the existence of stacking-fault-like phonon scatterers. No clear evidence for a scattering of phonons by tunneling states has been observed. If compared to previously reported measurements of the thermal conductivity of quasicrystals, these data indicate the very high structural perfection of this quasiperiodic material.This article is published as Gianno, K., A. V. Sologubenko, M. A. Chernikov, H. R. Ott, I. R. Fisher, and P. C. Canfield. "Low-temperature thermal conductivity of a single-grain Y-Mg-Zn icosahedral quasicrystal." Physical Review B 62, no. 1 (2000): 292. DOI: 10.1103/PhysRevB.62.292. Copyright 2000 American Physical Society. Posted with permission

Truncated BRPF1 Cooperates with Smoothened to Promote Adult Shh Medulloblastoma

The transition of neural progenitors to differentiated postmitotic neurons is mainly considered irreversible in physiological conditions. In the present work, we show that Shh pathway activation through SmoM2 expression promotes postmitotic neurons dedifferentiation, re-entering in the cell cycle and originating medulloblastoma in vivo. Notably, human adult patients present inactivating mutations of the chromatin reader BRPF1 that are associated with SMO mutations and absent in pediatric and adolescent patients. Here, we found that truncated BRPF1 protein, as found in human adult patients, is able to induce medulloblastoma in adult mice upon SmoM2 activation. Indeed, postmitotic neurons re-entered the cell cycle and proliferated as a result of chromatin remodeling of neurons by BRPF1. Our model of brain cancer explains the onset of a subset of human medulloblastoma in adult individuals where granule neuron progenitors are no longer present

Cerebellar liponeurocytoma: clinical, histopathological and molecular features of a series of three cases, including one recurrent tumor

Cerebellar liponeurocytoma (CL) is an unusual tumor, histologically composed of a mixture of small to medium-sized, rounded neurocytic cells and a variable lipomatous component. Although CL was originally considered as a subtype of medulloblastoma, subsequent molecular studies demonstrated that this tumor was a distinct entity, exhibiting the tumor protein p53 gene (TP53) missense mutations in 20% of cases, chromosome 17 deletion, and the absence of mutations in the adenomatous polyposis coli gene (APC), the protein patched homolog gene (PTCH), the kinase insert domain receptor gene (KDR), and the β-catenin gene (CTNNB). Apart from these molecular features, little is known about the pathogenesis and the genetic landscape of CL to date. In order to characterize the mutational landscape of CL and identify alterations that are driving tumorigenesis, we report a series of three cases, including one recurrent tumor, analysed by next-generation sequencing (NGS), which identified a total of 22 variants, of which four were missense mutations, nine were synonymous variants, and nine were located on intronic regions. In particular, DNA sequencing identified missense mutations in APC, KDR, and TP53 that could be implicated in promoting tumor progression and angiogenesis of CL. Furthermore, the NGS analysis revealed that recurrent CL did not have additional genetic changes compared with the primary tumor. Moreover, the high frequencies of detected mutations suggested that the identified alterations are germline variants. Indeed, an additional NGS on the genomic DNA obtained from one of the three patients confirmed the presence of the variants in the germline DNA. In conclusion, the obtained data support the hypothesis that CL is a distinct pathological entity that does not show specific somatic alterations driving tumorigenesis

Melanotic neuroectodermal tumor of infancy (Mnti) and pineal anlage tumor (pat) harbor a medulloblastoma signature by dna methylation profiling

none15MNTI is a rare tumor of indeterminate histogenesis and molecular signature. We performed methylation and copy number variation (CNV) profiles in patients with MNTI (n = 7) and PAT (n = 1) compared to the methylation brain tumor classifier v11b4 (BT-C) and the medulloblastoma (MB) classifier group 3/4 v1.0 (MB3/4-C). The patients’ mean age was 8 months (range: 4–48). The BT-C classified five MNTIs and one PAT (relapse) as class family MB-G3/G4, subclass group 3 (score: >0.9). The remaining two MNTIs and PAT (primary) were classified as class family plexus tumor, subclass pediatric (scores: >0.45). The MB3/4-C classified all MNTIs as high-risk MB-G3, Subtype II (score: >0.45). The primary PAT was classified as subtype III (score: 0.99) and its relapse as subtype II/III. MNTI and PAT clustered close to MB-G3. CNV analysis showed multiple rearrangements in one PAT and two MNTIs. The median follow-up was 54 months (four MNTIs in remission, one PAT died). In conclusion, we demonstrated that MNTI shares a homogenous methylation profile with MB-G3, and possibly with PAT. The role of a multipotent progenitor cell (i.e., early cranial neural crest cell) in their histogenesis and the influence of the anatomical site, tumor microenvironment, and other cytogenetic events in their divergent biologic behavior deserve further investigation.openLopez-Nunez O.; Alaggio R.; John I.; Ciolfi A.; Pedace L.; Mastronuzzi A.; Gianno F.; Giangaspero F.; Rossi S.; Donofrio V.; Cinalli G.; Surrey L.F.; Tartaglia M.; Locatelli F.; Miele E.Lopez-Nunez, O.; Alaggio, R.; John, I.; Ciolfi, A.; Pedace, L.; Mastronuzzi, A.; Gianno, F.; Giangaspero, F.; Rossi, S.; Donofrio, V.; Cinalli, G.; Surrey, L. F.; Tartaglia, M.; Locatelli, F.; Miele, E