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Sökning: WFRF:(Volckmann Richard)

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1.
  • Northcott, Paul A, et al. (författare)
  • Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.
  • 2014
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 511:7510, s. 428-428
  • Tidskriftsartikel (refereegranskat)abstract
    • Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.
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2.
  • Koppen, Arjen, et al. (författare)
  • Direct regulation of the minichromosome maintenance complex by MYCN in neuroblastoma
  • 2007
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 43:16, s. 2413-2422
  • Tidskriftsartikel (refereegranskat)abstract
    • The c-Myc and MYCN oncogenes strongly induce cell proliferation. Although a limited series of cell cycle genes were found to be induced by the myc transcription factors, it is still unclear how they mediate the proliferative phenotype. We therefore analysed a neuroblastoma cell line with inducible MYCN expression. We found that all members of the minichromosome maintenance complex (MCM2 - 7) and MCM8 and MCM10 were up-regulated by MYCN. Expression profiling of 110 neuroblastoma tumours revealed that these genes strongly correlated with MYCN expression in vivo. Extensive chromatin immunoprecipitation experiments were performed to investigate whether the MCM genes were primary MYCN targets. MYCN was bound to the proximal promoters of the MCM2 to -8 genes. These data suggest that MYCN stimulates the expression of not only MCM7, which is a well defined MYCN target gene, but also of the complete minichromosome maintenance complex. (c) 2007 Elsevier Ltd. All rights reserved.
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