Forskning ved Københavns Universitet - Københavns Universitet

Forside

The whole-genome landscape of medulloblastoma subtypes

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Dokumenter

  • Paul A. Northcott
  • Ivo Buchhalter
  • A. Sorana Morrissy
  • Volker Hovestadt
  • Tobias Ehrenberger
  • Susanne Gröbner
  • Maia Segura-Wang
  • Thomas Zichner
  • Vasilisa A. Rudneva
  • Hans Jörg Warnatz
  • Aaron H. Phillips
  • Steven Schumacher
  • Kortine Kleinheinz
  • Sebastian M. Waszak
  • Serap Erkek
  • David T.W. Jones
  • Barbara C. Worst
  • Marcel Kool
  • Marc Zapatka
  • Natalie Jäger
  • Lukas Chavez
  • Barbara Hutter
  • Matthias Bieg
  • Nagarajan Paramasivam
  • Michael Heinold
  • Zuguang Gu
  • Naveed Ishaque
  • Christina Jäger-Schmidt
  • Charles D. Imbusch
  • Alke Jugold
  • Daniel Hübschmann
  • Thomas Risch
  • Vyacheslav Amstislavskiy
  • Francisco German Rodriguez Gonzalez
  • Ursula D. Weber
  • Stephan Wolf
  • Giles W. Robinson
  • Xin Zhou
  • Gang Wu
  • David Finkelstein
  • Yanling Liu
  • Florence M.G. Cavalli
  • Betty Luu
  • Vijay Ramaswamy
  • Xiaochong Wu
  • Jan Koster
  • Marina Ryzhova
  • Yoon Jae Cho
  • Scott L. Pomeroy
  • Christel Herold-Mende
  • Martin Schuhmann
  • Martin Ebinger
  • Linda M. Liau
  • Jaume Mora
  • Roger E. McLendon
  • Nada Jabado
  • Toshihiro Kumabe
  • Eric Chuah
  • Yussanne Ma
  • Richard A. Moore
  • Andrew J. Mungall
  • Karen L. Mungall
  • Nina Thiessen
  • Kane Tse
  • Tina Wong
  • Steven J.M. Jones
  • Olaf Witt
  • Till Milde
  • Andreas Von Deimling
  • David Capper
  • Andrey Korshunov
  • Marie Laure Yaspo
  • Richard Kriwacki
  • Amar Gajjar
  • Jinghui Zhang
  • Rameen Beroukhim
  • Ernest Fraenkel
  • Jan O. Korbel
  • Benedikt Brors
  • Matthias Schlesner
  • Roland Eils
  • Marco A. Marra
  • Stefan M. Pfister
  • Michael D. Taylor
  • Peter Lichter

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.

OriginalsprogEngelsk
TidsskriftNature
Vol/bind547
Udgave nummer7663
Sider (fra-til)311-317
Antal sider7
ISSN0028-0836
DOI
StatusUdgivet - 19 jul. 2017

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