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The whole-genome landscape of medulloblastoma subtypes.

Publication ,  Journal Article
Northcott, PA; Buchhalter, I; Morrissy, AS; Hovestadt, V; Weischenfeldt, J; Ehrenberger, T; Gröbner, S; Segura-Wang, M; Zichner, T; Rudneva, VA ...
Published in: Nature
July 19, 2017

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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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

July 19, 2017

Volume

547

Issue

7663

Start / End Page

311 / 317

Location

England

Related Subject Headings

  • Wnt Proteins
  • Whole Genome Sequencing
  • Transcription Factors
  • Oncogenes
  • Mutation
  • Muscle Proteins
  • Molecular Targeted Therapy
  • Medulloblastoma
  • Humans
  • Genomics
 

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Northcott, P. A., Buchhalter, I., Morrissy, A. S., Hovestadt, V., Weischenfeldt, J., Ehrenberger, T., … Lichter, P. (2017). The whole-genome landscape of medulloblastoma subtypes. Nature, 547(7663), 311–317. https://doi.org/10.1038/nature22973
Northcott, Paul A., Ivo Buchhalter, A Sorana Morrissy, Volker Hovestadt, Joachim Weischenfeldt, Tobias Ehrenberger, Susanne Gröbner, et al. “The whole-genome landscape of medulloblastoma subtypes.Nature 547, no. 7663 (July 19, 2017): 311–17. https://doi.org/10.1038/nature22973.
Northcott PA, Buchhalter I, Morrissy AS, Hovestadt V, Weischenfeldt J, Ehrenberger T, et al. The whole-genome landscape of medulloblastoma subtypes. Nature. 2017 Jul 19;547(7663):311–7.
Northcott, Paul A., et al. “The whole-genome landscape of medulloblastoma subtypes.Nature, vol. 547, no. 7663, July 2017, pp. 311–17. Pubmed, doi:10.1038/nature22973.
Northcott PA, Buchhalter I, Morrissy AS, Hovestadt V, Weischenfeldt J, Ehrenberger T, Gröbner S, Segura-Wang M, Zichner T, Rudneva VA, Warnatz H-J, Sidiropoulos N, Phillips AH, Schumacher S, Kleinheinz K, Waszak SM, Erkek S, Jones DTW, Worst BC, Kool M, Zapatka M, Jäger N, Chavez L, Hutter B, Bieg M, Paramasivam N, Heinold M, Gu Z, Ishaque N, Jäger-Schmidt C, Imbusch CD, Jugold A, Hübschmann D, Risch T, Amstislavskiy V, Gonzalez FGR, Weber UD, Wolf S, Robinson GW, Zhou X, Wu G, Finkelstein D, Liu Y, Cavalli FMG, Luu B, Ramaswamy V, Wu X, Koster J, Ryzhova M, Cho Y-J, Pomeroy SL, Herold-Mende C, Schuhmann M, Ebinger M, Liau LM, Mora J, McLendon RE, Jabado N, Kumabe T, Chuah E, Ma Y, Moore RA, Mungall AJ, Mungall KL, Thiessen N, Tse K, Wong T, Jones SJM, Witt O, Milde T, Von Deimling A, Capper D, Korshunov A, Yaspo M-L, Kriwacki R, Gajjar A, Zhang J, Beroukhim R, Fraenkel E, Korbel JO, Brors B, Schlesner M, Eils R, Marra MA, Pfister SM, Taylor MD, Lichter P. The whole-genome landscape of medulloblastoma subtypes. Nature. 2017 Jul 19;547(7663):311–317.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

July 19, 2017

Volume

547

Issue

7663

Start / End Page

311 / 317

Location

England

Related Subject Headings

  • Wnt Proteins
  • Whole Genome Sequencing
  • Transcription Factors
  • Oncogenes
  • Mutation
  • Muscle Proteins
  • Molecular Targeted Therapy
  • Medulloblastoma
  • Humans
  • Genomics