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  The whole-genome landscape of medulloblastoma subtypes

Northcott, P. A., Buchhalter, I., Morrissy, A. S., Hovestadt, V., Weischenfeldt, J., Ehrenberger, T., et al. (2017). The whole-genome landscape of medulloblastoma subtypes. Nature, 547(7663), 311-317. doi:10.1038/nature22973.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-BC42-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-BC43-1
Genre: Journal Article

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© 2017 Macmillan Publishers Limited, part of Springer Nature

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Northcott, P. A., Author
Buchhalter, I., Author
Morrissy, A. S., Author
Hovestadt, V., Author
Weischenfeldt, J., Author
Ehrenberger, T., Author
Gröbner, S., Author
Segura-Wang, M., Author
Zichner, T., Author
Rudneva, V. A., Author
Warnatz, H. J.1, Author              
Sidiropoulos, N., Author
Phillips, A. H., Author
Schumacher, S., Author
Kleinheinz, K., Author
Waszak, S. M., Author
Erkek, S., Author
Jones, D. T. W., Author
Worst, B. C., Author
Kool, M., Author
Zapatka, M., AuthorJager, N., AuthorChavez, L., AuthorHutter, B., AuthorBieg, M., AuthorParamasivam, N., AuthorHeinold, M., AuthorGu, Z., AuthorIshaque, N., AuthorJager-Schmidt, C., AuthorImbusch, C. D., AuthorJugold, A., AuthorHubschmann, D., AuthorRisch, T., AuthorAmstislavskiy, V.1, Author              Gonzalez, F. G. R., AuthorWeber, U. D., AuthorWolf, S., AuthorRobinson, G. W., AuthorZhou, X., AuthorWu, G., AuthorFinkelstein, D., AuthorLiu, Y., AuthorCavalli, F. M. G., AuthorLuu, B., AuthorRamaswamy, V., AuthorWu, X., AuthorKoster, J., AuthorRyzhova, M., AuthorCho, Y. J., AuthorPomeroy, S. L., AuthorHerold-Mende, C., AuthorSchuhmann, M., AuthorEbinger, M., AuthorLiau, L. M., AuthorMora, J., AuthorMcLendon, R. E., AuthorJabado, N., AuthorKumabe, T., AuthorChuah, E., AuthorMa, Y., AuthorMoore, R. A., AuthorMungall, A. J., AuthorMungall, K. L., AuthorThiessen, N., AuthorTse, K., AuthorWong, T., AuthorJones, S. J. M., AuthorWitt, O., AuthorMilde, T., AuthorVon Deimling, A., AuthorCapper, D., AuthorKorshunov, A., AuthorYaspo, M. L.1, Author              Kriwacki, R., AuthorGajjar, A., AuthorZhang, J., AuthorBeroukhim, R., AuthorFraenkel, E., AuthorKorbel, J. O., AuthorBrors, B., AuthorSchlesner, M., AuthorEils, R., AuthorMarra, M. A., AuthorPfister, S. M., AuthorTaylor, M. D., AuthorLichter, P., 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              

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Free keywords: Carcinogenesis/genetics Carrier Proteins/genetics Cohort Studies DNA Methylation *DNA Mutational Analysis Datasets as Topic Epistasis, Genetic Genome, Human/*genetics Genomics Humans Medulloblastoma/*classification/*genetics Molecular Targeted Therapy Muscle Proteins/genetics Mutation Oncogenes/genetics Transcription Factors/genetics *Whole Genome Sequencing Wnt Proteins/genetics
 Abstract: Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.

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Language(s): eng - English
 Dates: 2017-05-102017-07-192017-07-20
 Publication Status: Published in print
 Pages: 7
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1038/nature22973
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: 547 (7663) Sequence Number: - Start / End Page: 311 - 317 Identifier: ISSN: 0028-0836
CoNE: https://pure.mpg.de/cone/journals/resource/954925427238