The forgotten foramina: a study of the anterior cribriform plate

CERVOXY CLINInternational audiencePurposeThe olfactory cleft has garnered interest since the advent of endoscopic skull base surgery. Its precise anatomy, however, is still partially unknown. According to Rouvière, an “ethmoidal foramen” is located in its antero-medial part and contains a process of the dura mater. In a more lateral and anterior location, a second foramen, the “cribroethmoidal foramen”, contains the anterior ethmoidal nerve. The aim of this study was to verify the existence of these elements and to establish landmarks for surgery.MethodsWe performed an anatomical and histological study of eight olfactory clefts in four cadavers using both endonasal endoscopic and endocranial dissection.ResultsAn ethmoidal and a cribroethmoidal foramen were found in, respectively, 100 and 75 % of cases. Their mean length was, respectively, 4.1 and 1.8 mm. They were located, respectively, in mean at 5.3 and 5.8 mm from the anterior ethmoidal artery.ConclusionOur anatomical study demonstrates the existence of both foramina. The ethmoidal foramen clearly represents an area of least resistance in the anterior part of the olfactory cleft, which could predispose to anterior skull base cerebrospinal fluid leaks and meningoceles

O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and low MGMT-encoded protein expression as prognostic markers in glioblastoma patients treated with biodegradable carmustine wafer implants after initial surgery followed by radiotherapy w

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Evidence for BRAF V600E and H3F3A K27M double mutations in paediatric glial and glioneuronal tumours

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Prognostic impact of the 2016 WHO classification of diffuse gliomas in the French POLA cohort

CERVOXY COLLInternational audienc

Histopathologic and Ultrastructural Features and Claudin Expression in Papillary Tumors of the Pineal Region

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PTPN11 mutations in canine and human disseminated histiocytic sarcoma

International audienceIn humans, histiocytic sarcoma (HS) is an aggressive cancer involving histiocytes. Its rarity and heterogeneity explain that treatment remains a challenge. Sharing high clinical and histopathological similarities with human HS, the canine HS is conversely frequent in specific breeds and thus constitutes a unique spontaneous model for human HS to decipher the genetic bases and to explore therapeutic options. We identified sequence alterations in the MAPK pathway in at least 63.9% (71/111) of HS cases with mutually exclusive BRAF (0.9%; 1/111), KRAS (7.2%; 8/111) and PTPN11 (56.75%; 63/111) mutations concentrated at hotspots common to human cancers. Recurrent PTPN11 mutations are associated to visceral disseminated HS subtype in dogs, the most aggressive clinical presentation. We then identified PTPN11 mutations in 3/19 (15.7%) human HS patients. Thus, we propose PTPN11 mutations as key events for a specific subset of human and canine HS the visceral disseminated form. Finally, by testing drugs targeting the MAPK pathway in eight canine HS cell lines, we identified a better anti-proliferation activity of MEK inhibitors than PTPN11 inhibitors in canine HS neoplastic cells. In combination, these results illustrate the relevance of naturally affected dogs in deciphering genetic mechanisms and selecting efficient targeted therapies for such rare and aggressive cancers in humans

A recurrent point mutation in PRKCA is a hallmark of chordoid gliomas

International audienceChordoid glioma (ChG) is a characteristic, slow growing, and well-circumscribed diencephalic tumor, whose mutational landscape is unknown. Here we report the analysis of 16 ChG by whole-exome and RNA-sequencing. We found that 15 ChG harbor the same PRKCA$^{D463H}$ mutation. PRKCA encodes the Protein kinase C (PKC) isozyme alpha (PKC$\alpha$) and is mutated in a wide range of human cancers. However the hot spot PRKCA$^{D463H}$ mutation was not described in other tumors. PRKCA$^{D463H}$ is strongly associated with the activation of protein translation initiation (EIF2) pathway. PKC$\alpha$$^{D463H}$ mRNA levels are more abundant than wild-type PKC$\alpha$ transcripts, whilePKC$\alpha$$^{D463H}$ is less stable than the PCK$\alpha$WT protein. Compared to PCK$\alpha$WT, the PKC$\alpha$$^{D463H}$ protein is depleted from the cell membrane. The PKC$\alpha$$^{D463H}$ mutant enhances proliferation of astrocytes and tanycytes, the cells of origin of ChG. In conclusion, our study identifies the hallmark mutation for chordoid gliomas and provides mechanistic insights on ChG oncogenesis

SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas

International audienceAnaplastic oligodendrogliomas (AOD) are rare glial tumors in adults with relative homogeneous clinical, radiological and histological features at the time of diagnosis but dramatically various clinical courses. Studies have identified several molecular abnormalities with clinical or biological relevance to AOD (e.g. t(1;19)(q10;p10), IDH1, IDH2, CIC and FUBP1 mutations).To better characterize the clinical and biological behavior of this tumor type, the creation of a national multicentric network, named "Prise en charge des OLigodendrogliomes Anaplasiques (POLA)," has been supported by the Institut National du Cancer (InCA). Newly diagnosed and centrally validated AOD patients and their related biological material (tumor and blood samples) were prospectively included in the POLA clinical database and tissue bank, respectively.At the molecular level, we have conducted a high-resolution single nucleotide polymorphism array analysis, which included 83 patients. Despite a careful central pathological review, AOD have been found to exhibit heterogeneous genomic features. A total of 82% of the tumors exhibited a 1p/19q-co-deletion, while 18% harbor a distinct chromosome pattern. Novel focal abnormalities, including homozygously deleted, amplified and disrupted regions, have been identified. Recurring copy neutral losses of heterozygosity (CNLOH) inducing the modulation of gene expression have also been discovered. CNLOH in the CDKN2A locus was associated with protein silencing in 1/3 of the cases. In addition, FUBP1 homozygous deletion was detected in one case suggesting a putative tumor suppressor role of FUBP1 in AOD.Our study showed that the genomic and pathological analyses of AOD are synergistic in detecting relevant clinical and biological subgroups of AOD