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  Active medulloblastoma enhancers reveal subgroup-specific cellular origins

Lin, C. Y., Erkek, S., Tong, Y., Yin, L., Federation, A. J., Zapatka, M., et al. (2016). Active medulloblastoma enhancers reveal subgroup-specific cellular origins. Nature, 530(7588), 57-62. doi:10.1038/nature16546.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-BC6A-6 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-BC6B-5
Genre: Journal Article

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© 2016 Macmillan Publishers Limited, part of Springer Nature
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 Creators:
Lin, C. Y., Author
Erkek, S., Author
Tong, Y., Author
Yin, L., Author
Federation, A. J., Author
Zapatka, M., Author
Haldipur, P., Author
Kawauchi, D., Author
Risch, T., Author
Warnatz, H. J.1, Author              
Worst, B. C., Author
Ju, B., Author
Orr, B. A., Author
Zeid, R., Author
Polaski, D. R., Author
Segura-Wang, M., Author
Waszak, S. M., Author
Jones, D. T., Author
Kool, M., Author
Hovestadt, V., Author
Buchhalter, I., AuthorSieber, L., AuthorJohann, P., AuthorChavez, L., AuthorGroschel, S., AuthorRyzhova, M., AuthorKorshunov, A., AuthorChen, W., AuthorChizhikov, V. V., AuthorMillen, K. J., AuthorAmstislavskiy, V.1, Author              Lehrach, H.2, Author              Yaspo, M. L.1, Author              Eils, R., AuthorLichter, P., AuthorKorbel, J. O., AuthorPfister, S. M., AuthorBradner, J. E., AuthorNorthcott, P. A., Author more..
Affiliations:
1Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2117287              
2Emeritus Group of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2385697              

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Free keywords: Animals Cerebellar Neoplasms/classification/*genetics/*pathology Enhancer Elements, Genetic/*genetics Female Gene Expression Regulation, Neoplastic/*genetics Gene Regulatory Networks/genetics Genes, Neoplasm/genetics Genes, Reporter/genetics Humans Male Medulloblastoma/*classification/genetics/*pathology Mice Reproducibility of Results Transcription Factors/*metabolism Zebrafish/genetics
 Abstract: Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating consequences on the developing child. Genomic studies have revealed four distinct molecular subgroups with divergent biology and clinical behaviour. An understanding of the regulatory circuitry governing the transcriptional landscapes of medulloblastoma subgroups, and how this relates to their respective developmental origins, is lacking. Here, using H3K27ac and BRD4 chromatin immunoprecipitation followed by sequencing (ChIP-seq) coupled with tissue-matched DNA methylation and transcriptome data, we describe the active cis-regulatory landscape across 28 primary medulloblastoma specimens. Analysis of differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity and revealed novel, clinically relevant insights into medulloblastoma biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors, validated by ChIP-seq, that is responsible for subgroup divergence, and implicates candidate cells of origin for Group 4. Our integrated analysis of enhancer elements in a large series of primary tumour samples reveals insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins.

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Language(s): eng - English
 Dates: 2016-01-272016-02-04
 Publication Status: Published in print
 Pages: 6
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1038/nature16546
ISSN: 1476-4687 (Electronic)0028-0836 (Print)
 Degree: -

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Title: Nature
  Abbreviation : Nature
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 530 (7588) Sequence Number: - Start / End Page: 57 - 62 Identifier: ISSN: 0028-0836
CoNE: /journals/resource/954925427238