Extrachromosomal DNA is Associated with Oncogene Amplification and Poor Outcome Across Multiple Cancers

Overview

Journal Nat Genet

Specialty Genetics

Date 2020 Aug 19

PMID 32807987

Citations 213

Authors

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

Affiliations

Soon will be listed here.

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.

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