001     120009
005     20240228135006.0
024 7 _ |a 10.1038/nature13379
|2 doi
024 7 _ |a pmid:25043047
|2 pmid
024 7 _ |a pmc:PMC4201514
|2 pmc
024 7 _ |a 0028-0836
|2 ISSN
024 7 _ |a 1476-4687
|2 ISSN
024 7 _ |a altmetric:2456657
|2 altmetric
037 _ _ |a DKFZ-2017-00597
041 _ _ |a eng
082 _ _ |a 070
100 1 _ |a Northcott, Paul A
|0 P:(DE-HGF)0
|b 0
|e First author
245 _ _ |a Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.
260 _ _ |a London [u.a.]
|c 2014
|b Nature Publ. Group52462
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1490694260_15176
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336 7 _ |a ARTICLE
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336 7 _ |a JOURNAL_ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.
536 _ _ |a 312 - Functional and structural genomics (POF3-312)
|0 G:(DE-HGF)POF3-312
|c POF3-312
|f POF III
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588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a DNA-Binding Proteins
|2 NLM Chemicals
650 _ 7 |a GFI1 protein, human
|2 NLM Chemicals
650 _ 7 |a GFI1B protein, human
|2 NLM Chemicals
650 _ 7 |a Proto-Oncogene Proteins
|2 NLM Chemicals
650 _ 7 |a Repressor Proteins
|2 NLM Chemicals
650 _ 7 |a Transcription Factors
|2 NLM Chemicals
700 1 _ |a Lee, Catherine
|b 1
700 1 _ |a Zichner, Thomas
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700 1 _ |a Stütz, Adrian M
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700 1 _ |a Erkek, Serap
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700 1 _ |a Shih, David J H
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700 1 _ |a Hovestadt, Volker
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700 1 _ |a Cavalli, Florence M G
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700 1 _ |a Zuyderduyn, Scott
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700 1 _ |a Bader, Gary D
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700 1 _ |a VandenBerg, Scott
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700 1 _ |a Wang, Wei
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773 _ _ |a 10.1038/nature13379
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