Details

Autor(en) / Beteiligte

• Rausch, Tobias
• Jones, David T.W.
• Zapatka, Marc
• Stütz, Adrian M.
• Zichner, Thomas
• Weischenfeldt, Joachim
• Jäger, Natalie
• Remke, Marc
• Shih, David
• Northcott, Paul A.
• Pfaff, Elke
• Tica, Jelena
• Wang, Qi
• Massimi, Luca
• Witt, Hendrik
• Bender, Sebastian
• Pleier, Sabrina
• Cin, Huriye
• Hawkins, Cynthia
• Beck, Christian
• von Deimling, Andreas
• Hans, Volkmar
• Brors, Benedikt
• Eils, Roland
• Scheurlen, Wolfram
• Blake, Jonathon
• Benes, Vladimir
• Kulozik, Andreas E.
• Witt, Olaf
• Martin, Dianna
• Zhang, Cindy
• Porat, Rinnat
• Merino, Diana M.
• Wasserman, Jonathan
• Jabado, Nada
• Fontebasso, Adam
• Bullinger, Lars
• Rücker, Frank G.
• Döhner, Konstanze
• Döhner, Hartmut
• Koster, Jan
• Molenaar, Jan J.
• Versteeg, Rogier
• Kool, Marcel
• Tabori, Uri
• Malkin, David
• Korshunov, Andrey
• Taylor, Michael D.
• Lichter, Peter
• Pfister, Stefan M.
• Korbel, Jan O.

Titel

Genome Sequencing of Pediatric Medulloblastoma Links Catastrophic DNA Rearrangements with TP53 Mutations

Ist Teil von

• Cell, 2012-01, Vol.148 (1-2), p.59-71

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2012

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Genomic rearrangements are thought to occur progressively during tumor development. Recent findings, however, suggest an alternative mechanism, involving massive chromosome rearrangements in a one-step catastrophic event termed chromothripsis. We report the whole-genome sequencing-based analysis of a Sonic-Hedgehog medulloblastoma (SHH-MB) brain tumor from a patient with a germline TP53 mutation (Li-Fraumeni syndrome), uncovering massive, complex chromosome rearrangements. Integrating TP53 status with microarray and deep sequencing-based DNA rearrangement data in additional patients reveals a striking association between TP53 mutation and chromothripsis in SHH-MBs. Analysis of additional tumor entities substantiates a link between TP53 mutation and chromothripsis, and indicates a context-specific role for p53 in catastrophic DNA rearrangements. Among these, we observed a strong association between somatic TP53 mutations and chromothripsis in acute myeloid leukemia. These findings connect p53 status and chromothripsis in specific tumor types, providing a genetic basis for understanding particularly aggressive subtypes of cancer. [Display omitted] ► Complex chromosomal alterations (chromothripsis) observed in medulloblastomas ► Cancers with such alterations harbor TP53 mutations ► Context-specific link between the status of p53 and likelihood of chromothripsis ► p53 status and chromothripsis also correlate with aggressive acute myeloid leukemia Connecting p53 status and chromothripsis in specific types of cancer provides a genetic basis for the more aggressive forms of medulloblastoma and leukemia.