Journal article
Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis
K Nones, N Waddell, N Wayte, AM Patch, P Bailey, F Newell, O Holmes, JL Fink, MCJ Quinn, YH Tang, G Lampe, K Quek, KA Loffler, S Manning, S Idrisoglu, D Miller, Q Xu, N Waddell, PJ Wilson, TJC Bruxner Show all
Nature Communications | Published : 2014
DOI: 10.1038/ncomms6224
Abstract
Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chrom..
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Grants
Awarded by Australian Research Council
Funding Acknowledgements
This work was supported by funding from the Australian National Health and Medical Research Council (NHMRC-grant APP1021403 and 631701) and Smart Futures National and International Research Alliances Program (2008004333). S. M. G. was an Australian National Health and Medical Research Council Principal Research Fellow (1025427). D. C. W. is supported by Future Fellowship from the Australian Research Council. N.K.H. is supported by NHMRC Senior Principal Research Fellowship. P. T. S. is supported by a fellowship from The National Breast Cancer Foundation, Australia. We thank Deborah Gwynne for central co-ordination at the Queensland Centre for Medical Genomics; and Janine Thomas for maintaining the clinical database.