32 research outputs found

    A distinct spectrum of copy number aberrations in pediatric high-grade gliomas

    Get PDF
    As genome-scale technologies begin to unravel the complexity of the equivalent tumors in adults, we can attempt detailed characterization of high-grade gliomas in children, that have until recently been lacking. Toward this end, we sought to validate and extend investigations of the differences between pediatric and adult tumors. Purpose: As genome-scale technologies begin to unravel the complexity of the equivalent tumors in adults, we can attempt detailed characterization of high-grade gliomas in children, that have until recently been lacking. Toward this end, we sought to validate and extend investigations of the differences between pediatric and adult tumors. Experimental Design: We carried out copy number profiling by array comparative genomic hybridization using a 32K bacterial artificial chromosome platform on 63 formalin-fixed paraffin-embedded cases of high-grade glioma arising in children and young people (<23 years). Results: The genomic profiles of these tumors could be subclassified into four categories: those with stable genomes, which were associated with a better prognosis; those with aneuploid and those with highly rearranged genomes; and those with an amplifier genotype, which had a significantly worse clinical outcome. Independent of this was a clear segregation of cases with 1q gain (more common in children) from those with concurrent 7 gain/10q loss (a defining feature of adults). Detailed mapping of all the amplification and deletion events revealed numerous low-frequency amplifications, including IGF1R, PDGFRB, PIK3CA, CDK6, CCND1, and CCNE1, and novel homozygous deletions encompassing unknown genes, including those at 5q35, 10q25, and 22q13. Despite this, aberrations targeting the “core signaling pathways” in adult glioblastomas are significantly underrepresented in the pediatric setting. Conclusions: These data highlight that although there are overlaps in the genomic events driving gliomagenesis of all ages, the pediatric disease harbors a distinct spectrum of copy number aberrations compared with adults.National Health Service funding to the NIHR Biomedical Research Centre. This work was supported by The Royal Marsden Children's Department Fund, Fundação para a Ciência e Tecnologia, Portugal, and Breakthrough Breast Cance

    Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development.

    Get PDF
    Although paediatric high grade gliomas resemble their adult counterparts in many ways, there appear to be distinct clinical and biological differences. One important factor hampering the development of new targeted therapies is the relative lack of cell lines derived from childhood glioma patients, as it is unclear whether the well-established adult lines commonly used are representative of the underlying molecular genetics of childhood tumours. We have carried out a detailed molecular and phenotypic characterisation of a series of paediatric high grade glioma cell lines in comparison to routinely used adult lines

    Microphytobenthos of Arctic Kongsfjorden (Svalbard, Norway): biomass and potential primary production along the shore line

    Get PDF
    During summer 2007, Arctic microphytobenthic potential primary production was measured at several stations around the coastline of Kongsfjorden (Svalbard, Norway) at ?5 m water depth and at two stations at five different water depths (5, 10, 15, 20, 30 m). Oxygen planar optode sensor spots were used ex situ to determine oxygen exchange in the overlying water of intact sediment cores under controlled light (ca. 100 ?mol photons m?2 s?1) and temperature (2–4°C) conditions. Patches of microalgae (mainly diatoms) covering sandy sediments at water depths down to 30 m showed high biomass of up to 317 mg chl a m?2. In spite of increasing water depth, no significant trend in “photoautotrophic active biomass” (chl a, ratio living/dead cells, cell sizes) and, thus, in primary production was measured at both stations. All sites from ?5 to 30 m water depth exhibited variable rates of net production from ?19 to +40 mg O2 m?2 h?1 (?168 to +360 mg C m?2 day?1) and gross production of about 2–62 mg O2 m?2 h?1 (17–554 mg C m?2 day?1), which is comparable to other polar as well as temperate regions. No relation between photoautotrophic biomass and gross/net production values was found. Microphytobenthos demonstrated significant rates of primary production that is comparable to pelagic production of Kongsfjorden and, hence, emphasised the importance as C source for the zoobenthos

    Kellerhals Jean (Recueil d'études introduites par), « Le juste : normes et idéaux », L'Année sociologique, vol. 45, n° 2, 1995

    Full text link
    Kourilsky-Augeven Chantal. Kellerhals Jean (Recueil d'études introduites par), « Le juste : normes et idéaux », L'Année sociologique, vol. 45, n° 2, 1995. In: Droit et société, n°36-37, 1997. On Side of a Dialogue. Exemples actuels de Socio-Legal Studies au Royaume-Uni. pp. 486-489
    corecore