Genome sequencing of childhood medulloblastoma brain tumors links chromothripsis with TP53 mutations

·发布 2012年1月20日 ·更新 2014年5月4日

样本数

实验数

芯片平台

实验描述

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'. 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 GSE21140. 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.

芯片平台

A-AFFY-107

Affymetrix GeneChip Human Mapping 250K Array Nsp [Mapping250K_Nsp]（11 例）

A-AFFY-142

Affymetrix GeneChip Genome-Wide Human SNP 6.0 [GenomeWideSNP_6]（38 例）

样本属性

disease state

medulloblastoma

gender

F, M

Organism

Homo sapiens

sample id

2002, 2004, 2005, 2012, 2016, 2017, 2018, 2019, 2020, 2024, 2031, 2034, 2035, 2037, 2038, 2039, 2040, 2046, 2050, 361, 383, 387, 391, 460, 462, 463, 471, 486, 496, 518

tissue

blood, medulloblastoma tumor

实验信息

登记号

E-GEOD-34258

GEO 编号

GSE34258

实验类型

comparative genomic hybridization by array

物种

Homo sapiens

发布日期

2012年1月20日

更新日期

2014年5月4日

提交者

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

外部链接

ArrayExpress 原始页 NCBI GEO：GSE34258

分析服务

Genome sequencing of childhood medulloblastoma brain tumors links chromothripsis with TP53 mutations

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