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Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers

Item Type:Article
Title:Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers
Creators Name:Kim, H. and Nguyen, N.P. and Turner, K. and Wu, S. and Gujar, A.D. and Luebeck, J. and Liu, J. and Deshpande, V. and Rajkumar, U. and Namburi, S. and Amin, S.B. and Yi, E. and Menghi, F. and Schulte, J.H. and Henssen, A.G. and Chang, H.Y. and Beck, C.R. and Mischel, .S. and Bafna, V. and Verhaak, R.G.W.
Abstract:Extrachromosomal DNA (ecDNA) amplification promotes intratumoral genetic heterogeneity and accelerated tumor evolution; however, its frequency and clinical impact are unclear. Using computational analysis of whole-genome sequencing data from 3,212 cancer patients, we show that ecDNA amplification frequently occurs in most cancer types but not in blood or normal tissue. Oncogenes were highly enriched on amplified ecDNA, and the most common recurrent oncogene amplifications arose on ecDNA. EcDNA amplifications resulted in higher levels of oncogene transcription compared to copy number-matched linear DNA, coupled with enhanced chromatin accessibility, and more frequently resulted in transcript fusions. Patients whose cancers carried ecDNA had significantly shorter survival, even when controlled for tissue type, than patients whose cancers were not driven by ecDNA-based oncogene amplification. The results presented here demonstrate that ecDNA-based oncogene amplification is common in cancer, is different from chromosomal amplification and drives poor outcome for patients across many cancer types.
Keywords:Chromatin, Chromosomes, DNA, Gene Amplification, Neoplasms, Oncogenes, Tumor Cell Line
Source:Nature Genetics
Publisher:Nature Publishing Group
Page Range:891-897
Date:September 2020
Additional Information:Copyright © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
Official Publication:https://doi.org/10.1038/s41588-020-0678-2
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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