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

Hoon Kim, Nam-Phuong Nguyen, Kristen Turner, Sihan Wu, Amit D. Gujar, Jens Luebeck, Jihe Liu, Viraj Deshpande, Utkrisht Rajkumar, Sandeep Namburi, Samirkumar B. Amin, Eunhee Yi, Francesca Menghi, Johannes H. Schulte, Anton G. Henssen, Howard Y. Chang, Christine R. Beck, Paul S. Mischel*, Vineet Bafna*, Roel G. W. Verhaak*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Extrachromosomal DNA (ecDNA) amplification promotes intratumoral genetic heterogeneity and accelerated tumor evolution1–3; 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.
Original languageEnglish
Pages (from-to)891-897
Number of pages7
JournalNature Genetics
Issue number9
Publication statusPublished - Sep 2020

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