Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers.
Document Type
Article
Publication Date
9-1-2020
Keywords
JGM, JAXCC, Cell Line, Tumor, Chromatin, Chromosomes, DNA, Gene Amplification, Humans, Neoplasms, Oncogenes
JAX Source
Nat Genet 2020 Sep; 52(9):891-97
Volume
52
Issue
9
First Page
891
Last Page
897
ISSN
1546-1718
PMID
32807987
DOI
https://doi.org/10.1038/s41588-020-0678-2
Grant
CA034196
Abstract
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.
Recommended Citation
Kim H,
Nguyen N,
Turner K,
Wu S,
Gujar A,
Luebeck J,
Liu J,
Deshpande V,
Rajkumar U,
Namburi S,
Amin S,
Yi E,
Menghi F,
Schulte J,
Henssen A,
Chang H,
Beck C,
Mischel P,
Bafna V,
Verhaak R.
Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers. Nat Genet 2020 Sep; 52(9):891-97