Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers.
Nat Genet
; 52(9): 891-897, 2020 09.
Article
en En
| MEDLINE
| ID: mdl-32807987
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Oncogenes
/
ADN
/
Amplificación de Genes
/
Cromosomas
/
Neoplasias
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos