Title

Extrachromosomal oncogene amplification in tumour pathogenesis and evolution.

Document Type

Article

Publication Date

3-14-2019

Keywords

JGM

JAX Source

Nat Rev Cancer 2019 Mar 14 [Epub ahead of print]

PMID

30872802

DOI

https://doi.org/10.1038/s41568-019-0128-6

Grant

CA190121,CA034196,Musella Foundation, B*CURED Foundation

Abstract

Recent reports have demonstrated that oncogene amplification on extrachromosomal DNA (ecDNA) is a frequent event in cancer, providing new momentum to explore a phenomenon first discovered several decades ago. The direct consequence of ecDNA gains in these cases is an increase in DNA copy number of the oncogenes residing on the extrachromosomal element. A secondary effect, perhaps even more important, is that the unequal segregation of ecDNA from a parental tumour cell to offspring cells rapidly increases tumour heterogeneity, thus providing the tumour with an additional array of responses to microenvironment-induced and therapy-induced stress factors and perhaps providing an evolutionary advantage. This Perspectives article discusses the current knowledge and potential implications of oncogene amplification on ecDNA in cancer.

Comments

The authors thank C. Beck (Jackson Laboratory for Genomic Medicine), S. Wu and K. M. Turner (Mischel laboratory) for feedback on the manuscript content and S. Cassidy (Jackson Laboratory for Genomic Medicine) for support in manuscript writing.

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