Dataset Information

Ena-DATASET-UCL-ICH-25-11-2015-12:32:35:398-26 - samples

ABSTRACT: Description not provided

PROVIDER: EGAD00001001687 | EGA |

REPOSITORIES: EGA

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Publications

Telomerase activation by genomic rearrangements in high-risk neuroblastoma.

Peifer Martin M Hertwig Falk F Roels Frederik F Dreidax Daniel D Gartlgruber Moritz M Menon Roopika R Krämer Andrea A Roncaioli Justin L JL Sand Frederik F Heuckmann Johannes M JM Ikram Fakhera F Schmidt Rene R Ackermann Sandra S Engesser Anne A Kahlert Yvonne Y Vogel Wenzel W Altmüller Janine J Nürnberg Peter P Thierry-Mieg Jean J Thierry-Mieg Danielle D Mariappan Aruljothi A Heynck Stefanie S Mariotti Erika E Henrich Kai-Oliver KO Gloeckner Christian C Bosco Graziella G Leuschner Ivo I Schweiger Michal R MR Savelyeva Larissa L Watkins Simon C SC Shao Chunxuan C Bell Emma E Höfer Thomas T Achter Viktor V Lang Ulrich U Theissen Jessica J Volland Ruth R Saadati Maral M Eggert Angelika A de Wilde Bram B Berthold Frank F Peng Zhiyu Z Zhao Chen C Shi Leming L Ortmann Monika M Büttner Reinhard R Perner Sven S Hero Barbara B Schramm Alexander A Schulte Johannes H JH Herrmann Carl C O'Sullivan Roderick J RJ Westermann Frank F Thomas Roman K RK Fischer Matthias M

Nature 20151014 7575

Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affectin ...[more]

PMID: 26466568

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Project description:FMRFamide-like peptide (FLP) signalling systems are core to nematode neuromuscular function. Novel drug discovery efforts associated with nematode FLP/FLP receptor biology are advanced through the accumulation of basic biological data that can reveal subtle complexities within the neuropeptidergic system. This study reports the characterisation of FMRFamide-like peptide encoding gene-11 (flp-11) and FMRFamide-like peptide encoding gene-32 (flp-32), two distinct flp genes which encode the analogous peptide, AMRN(A/S)LVRFamide, in multiple nematode species - the only known example of this phenomenon within the FLPergic system of nematodes. Using bioinformatics, in situ hybridisation, immunocytochemistry and behavioural assays we show that: (i) flp-11 and -32 are distinct flp genes expressed individually or in tandem across multiple nematode species, where they encode a highly similar peptide; (ii) flp-11 does not appear to be the most widely expressed flp in Caenorhabditis elegans; (iii) in species expressing both flp-11 and flp-32, flp-11 displays a conserved, restricted expression pattern across nematode clades and lifestyles; (iv) in species expressing both flp-11 and flp-32, flp-32 expression is more widespread and less conserved than flp-11; (v) in species expressing only flp-11, the flp-11 expression profile is more similar to the flp-32 profile observed in species expressing both; and (vi) FLP-11 peptides inhibit motor function in multiple nematode species. The biological significance and evolutionary origin of flp-11 and -32 peptide duplication remains unclear despite attempts to identify a common ancestor; this may become clearer as the availability of genomic data improves. This work provides insight into the complexity of the neuropeptidergic system in nematodes, and begins to examine how nematodes may compensate for structural neuronal simplicity. From a parasite control standpoint, this work underscores the importance of basic biological data, and has wider implications for the utility of C. elegans as a model for parasite neurobiology.

Dataset Information

Ena-DATASET-UCL-ICH-25-11-2015-12:32:35:398-26 - samples

Publications

Telomerase activation by genomic rearrangements in high-risk neuroblastoma.

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