Chromothripsis-like patterns are recurring but heterogeneously distributed features in a survey of 22,347 cancer genome screens

BMC Genomics

Research Article

Homayoun C Bagheri¹  Michael Baudis²  Nitin Kumar²  Christian von Mering²  Mark D Robinson²  Haoyang Cai² 

[1] Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland;Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland;Swiss Institute of Bioinformatics, University of Zurich, Zurich, Switzerland;

关键词: Chromothripsis;    Human cancer;    Array comparative genomic hybridization;    SNP array;   

DOI  :  10.1186/1471-2164-15-82

 received in 2013-08-09, accepted in 2014-01-10,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundChromothripsis is a recently discovered phenomenon of genomic rearrangement, possibly arising during a single genome-shattering event. This could provide an alternative paradigm in cancer development, replacing the gradual accumulation of genomic changes with a “one-off” catastrophic event. However, the term has been used with varying operational definitions, with the minimal consensus being a large number of locally clustered copy number aberrations. The mechanisms underlying these chromothripsis-like patterns (CTLP) and their specific impact on tumorigenesis are still poorly understood.ResultsHere, we identified CTLP in 918 cancer samples, from a dataset of more than 22,000 oncogenomic arrays covering 132 cancer types. Fragmentation hotspots were found to be located on chromosome 8, 11, 12 and 17. Among the various cancer types, soft-tissue tumors exhibited particularly high CTLP frequencies. Genomic context analysis revealed that CTLP rearrangements frequently occurred in genomes that additionally harbored multiple copy number aberrations (CNAs). An investigation into the affected chromosomal regions showed a large proportion of arm-level pulverization and telomere related events, which would be compatible to a number of underlying mechanisms. We also report evidence that these genomic events may be correlated with patient age, stage and survival rate.ConclusionsThrough a large-scale analysis of oncogenomic array data sets, this study characterized features associated with genomic aberrations patterns, compatible to the spectrum of “chromothripsis”-definitions as previously used. While quantifying clustered genomic copy number aberrations in cancer samples, our data indicates an underlying biological heterogeneity behind these chromothripsis-like patterns, beyond a well defined “chromthripsis” phenomenon.

【 授权许可】

Unknown   
© Cai et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.