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Series GSE34258 Query DataSets for GSE34258
Status Public on Jan 20, 2012
Title Genome sequencing of childhood medulloblastoma brain tumors links chromothripsis with TP53 mutations
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
Summary Genomic rearrangements typically occur progressively during tumor development. Recent findings, however, suggest an alternative mechanism, involving chromosome shattering and reshuffling ('chromothripsis'), for which no genetic basis has yet been described. Whole-genome sequencing of a Sonic-Hedgehog medulloblastoma (SHH-MB) brain tumor from a patient with a germline TP53 mutation (Li-Fraumeni syndrome) revealed massive, complex rearrangements resulting from chromothripsis. Integrating TP53 status with genomic rearrangement data in additional medulloblastomas revealed a striking association between TP53 mutation and chromothripsis in SHH-MBs. Unexpectedly, five seemingly sporadic SHH-MB patients with chromothripsis harbored TP53 germline mutations – findings relevant for clinical management. Analysis of additional tumor entities substantiated a link between TP53 mutation and chromothripsis, beyond general genomic instability. Among these, we observed a strong association between somatic TP53 mutations and chromothripsis in acute myeloid leukemia. These findings implicate p53 in the initiation of, or cellular reaction to, chromothripsis – a novel role for the 'guardian of the genome'.
Overall design The DNA copy-number profiles of 11 primary medulloblastoma samples were analyzed on the Affymetrix Mapping250K Nsp array, together with data from 70 primary samples taken from GSE14437. Data from diploid reference samples were taken from GSE9222. Additionally, DNA copy-number profiles for 19 additional medulloblastoma samples were generated on the Affymetrix SNP6 platform with matched blood samples.
Contributor(s) Rausch T, Jones DT, Zapatka M, Stütz AM, Zichner T, Weischenfeldt J, Jäger N, Remke M, Shih D, Northcott PA, Pfaff E, Tica J, Wang Q, Massimi L, Witt H, Bender S, Pleier S, Cin H, Hawkins C, Beck C, von Deimling A, Hans V, Brors B, Eils R, Scheurlen W, Blake J, Benes V, Kulozik AE, Witt O, Martin D, Zhang C, Porat R, Merino D, Wasserman J, Jabado N, Fontebasso A, Bullinger L, Rücker F, Döhner K, Döhner H, Koster J, Molenaar JJ, Versteeg R, Kool M, Tabori U, Malkin D, Korshunov A, Taylor MD, Lichter P
Citation(s) 22265402
Submission date Dec 08, 2011
Last update date Nov 27, 2018
Contact name David J. H. Shih
Phone (416) 813-7654
Organization name Hospital for Sick Children
Department Developmental and Stem Cell Biology
Lab Peter Gilgan Centre for Research and Learning
Street address 686 Bay St
City Toronto
State/province ON
ZIP/Postal code M5G 0A4
Country Canada
Platforms (2)
GPL3718 [Mapping250K_Nsp] Affymetrix Mapping 250K Nsp SNP Array
GPL6801 [GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array
Samples (49)
GSM846007 medulloblastoma tumor MB-361
GSM846008 medulloblastoma tumor MB-383
GSM846009 medulloblastoma tumor MB-387
BioProject PRJNA149743

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Supplementary file Size Download File type/resource
GSE34258_RAW.tar 1.4 Gb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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