Pilocytic astrocytoma of the optic pathway: a tumour deriving from radial glia cells with a specific gene signature.

Pilocytic astrocytomas are WHO grade I gliomas that occur predominantly in childhood. They share features of both astroglial and oligodendroglial lineages. These tumours affect preferentially the cerebellum (benign clinical course) and the optic pathway, especially the hypothalamo-chiasmatic region (poor prognosis). Understanding the molecular basis responsible for the aggressive behaviour of hypothalamo-chiasmatic pilocytic astrocytomas is a prerequisite to setting up new molecular targeted therapies. We used the microarray technique to compare the transcriptional profiles of five hypothalamo-chiasmatic and six cerebellar pilocytic astrocytomas. Validation of the microarray results and comparison of the tumours with normal developing tissue was done by quantitative real-time PCR and immunohistochemistry. Results demonstrate that cerebellar and hypothalamo-chiasmatic pilocytic astrocytomas are two genetically distinct and topography-dependent entities. Numerous genes upregulated in hypothalamo-chiasmatic pilocytic astrocytomas also increased in the developing chiasm, suggesting that developmental genes mirror the cell of origin whereas migrative, adhesive and proliferative genes reflect infiltrative properties of these tumours. Of particular interest, NOTCH2, a gene expressed in radial glia and involved in gliomagenesis, was upregulated in hypothalamo-chiasmatic pilocytic astrocytomas. In order to find progenitor cells that could give rise to hypothalamo-chiasmatic pilocytic astrocytomas, we performed a morphological study of the hypothalamo-chiasmatic region and identified, in the floor of the third ventricle, a unique population of vimentin- and glial fibrillary acidic protein-positive cells highly suggestive of radial glia cells. Therefore, pilocytic astrocytomas of the hypothalamo-chiasmatic region should be considered as a distinct entity which probably originates from a unique population of cells with radial glia phenotype.

Thalamic gliomas in children: an extensive clinical, neuroradiological and pathological study of 14 cases.

OBJECT: Thalamic tumors represent only 1 to 5% of brain neoplasms but frequently affect children. However, pediatric series are rare and go back to several years in spite of recent advances in the neuroradiological, pathological, and molecular fields. METHODS: We report a series of 14 pediatric thalamic gliomas with clinical, neuroradiological, and pathological studies including p53 immunostaining in 11 cases and 1p19q status in three cases. RESULTS: Our series included five pilocytic astrocytomas, seven oligodendrogliomas, and two glioblastomas. Pilocytic astrocytomas were characterized by strong contrast enhancement, lack of p53 expression, and excellent prognosis. Oligodendrogliomas frequently demonstrated an aspect of unilateral thalamic enlargement lacking or with slight contrast enhancement. Some of them expressed p53 or demonstrated 1p loss. Anaplastic oligodendrogliomas and glioblastomas displayed a poor outcome, with a mean survival of 8 months after surgery. CONCLUSION: Our series of pediatric thalamic gliomas clearly distinguishes pilocytic astrocytomas from anaplastic oligodendrogliomas regarding neuroimaging, pathology, and prognosis.

Vanadium-dependent iodoperoxidases in Laminaria digitata, a novel biochemical function diverging from brown algal bromoperoxidases.

The brown alga Laminaria digitata features a distinct vanadium-dependent iodoperoxidase (vIPO) activity, which has been purified to electrophoretic homogeneity. Steady-state analyses at pH 6.2 are reported for vIPO (K (m) (I-) = 2.5 mM; k (cat) (I-) = 462 s(-1)) and for the previously characterised vanadium-dependent bromoperoxidase in L. digitata (K (m) (I-) =18.1 mM; k (cat) (I-) = 38 s(-1)). Although the vIPO enzyme specifically oxidises iodide, competition experiments with halides indicate that bromide is a competitive inhibitor with respect to the fixation of iodide. A full-length complementary ANA (cDNA) was cloned and shown to be actively transcribed in L. digitata and to encode the vIPO enzyme. Mass spectrometry analyses of tryptic digests of vIPO indicated the presence of at least two very similar proteins, in agreement with Southern analyses showing that vIPOs are encoded by a multigenic family in L. digitata. Phylogenetic analyses indicated that vIPO shares a close common ancestor with brown algal vanadium-dependent bromoperoxidases. Based on a three-dimensional structure model of the vIPO active site and on comparisons with those of other vanadium-dependent haloperoxidases, we propose a hypothesis to explain the evolution of strict specificity for iodide in L. digitata vIPO.