%0 Journal Article %1 Rausch2012 %A Rausch, Tobias %A Jones, David T W. %A Zapatka, Marc %A Stütz, Adrian M. %A Zichner, Thomas %A Weischenfeldt, Joachim %A Jäger, Natalie %A Remke, Marc %A Shih, David %A Northcott, Paul A. %A Pfaff, Elke %A Tica, Jelena %A Wang, Qi %A Massimi, Luca %A Witt, Hendrik %A Bender, Sebastian %A Pleier, Sabrina %A Cin, Huriye %A Hawkins, Cynthia %A Beck, Christian %A von Deimling, Andreas %A Hans, Volkmar %A Brors, Benedikt %A Eils, Roland %A Scheurlen, Wolfram %A Blake, Jonathon %A Benes, Vladimir %A Kulozik, Andreas E. %A Witt, Olaf %A Martin, Dianna %A Zhang, Cindy %A Porat, Rinnat %A Merino, Diana M. %A Wasserman, Jonathan %A Jabado, Nada %A Fontebasso, Adam %A Bullinger, Lars %A Rücker, Frank G. %A Döhner, Konstanze %A Döhner, Hartmut %A Koster, Jan %A Molenaar, Jan J. %A Versteeg, Rogier %A Kool, Marcel %A Tabori, Uri %A Malkin, David %A Korshunov, Andrey %A Taylor, Michael D. %A Lichter, Peter %A Pfister, Stefan M. %A Korbel, Jan O. %D 2012 %J Cell %K Aberrations; Acute, Aged; Analysis; Animal; Animals; Brain Child; Chromosome Copy DNA Disease Gene Humans; Leukemia, Li-Fraumeni Medulloblastoma, Mice; Middle Models, Mutational Myeloid, Neoplasms, Number Protein Rearrangement; Suppressor Syndrome, Tumor Variations; genetics genetics; p53, physiopathology; %N 1-2 %P 59--71 %R 10.1016/j.cell.2011.12.013 %T Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. %U http://dx.doi.org/10.1016/j.cell.2011.12.013 %V 148 %X 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.

@article{Rausch2012, __markedentry = {[bbrors:6]}, abstract = {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.}, added-at = {2015-04-09T12:36:21.000+0200}, author = {Rausch, Tobias and Jones, David T W. and Zapatka, Marc and St{\"{u}}tz, Adrian M. and Zichner, Thomas and Weischenfeldt, Joachim and J{\"{a}}ger, Natalie and Remke, Marc and Shih, David and Northcott, Paul A. and Pfaff, Elke and Tica, Jelena and Wang, Qi and Massimi, Luca and Witt, Hendrik and Bender, Sebastian and Pleier, Sabrina and Cin, Huriye and Hawkins, Cynthia and Beck, Christian and {von Deimling}, Andreas and Hans, Volkmar and Brors, Benedikt and Eils, Roland and Scheurlen, Wolfram and Blake, Jonathon and Benes, Vladimir and Kulozik, Andreas E. and Witt, Olaf and Martin, Dianna and Zhang, Cindy and Porat, Rinnat and Merino, Diana M. and Wasserman, Jonathan and Jabado, Nada and Fontebasso, Adam and Bullinger, Lars and R{\"{u}}cker, Frank G. and D{\"{o}}hner, Konstanze and D{\"{o}}hner, Hartmut and Koster, Jan and Molenaar, Jan J. and Versteeg, Rogier and Kool, Marcel and Tabori, Uri and Malkin, David and Korshunov, Andrey and Taylor, Michael D. and Lichter, Peter and Pfister, Stefan M. and Korbel, Jan O.}, biburl = {https://www.bibsonomy.org/bibtex/26cd19fb72697f069a98f1b00e4d7fb5d/bbrors}, doi = {10.1016/j.cell.2011.12.013}, institution = {European Molecular Biology Laboratory, Meyerhofstr. 1, 69117 Heidelberg, Germany.}, interhash = {2263f609d937305460ff390882934e00}, intrahash = {6cd19fb72697f069a98f1b00e4d7fb5d}, journal = {Cell}, keywords = {Aberrations; Acute, Aged; Analysis; Animal; Animals; Brain Child; Chromosome Copy DNA Disease Gene Humans; Leukemia, Li-Fraumeni Medulloblastoma, Mice; Middle Models, Mutational Myeloid, Neoplasms, Number Protein Rearrangement; Suppressor Syndrome, Tumor Variations; genetics genetics; p53, physiopathology;}, language = {eng}, medline-pst = {ppublish}, month = Jan, number = {1-2}, owner = {bbrors}, pages = {59--71}, pii = {S0092-8674(11)01516-9}, pmid = {22265402}, timestamp = {2015-04-09T12:36:21.000+0200}, title = {Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations.}, url = {http://dx.doi.org/10.1016/j.cell.2011.12.013}, volume = 148, year = 2012 }