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Extrachromosomal DNA d relieving heredity constraints, accelerating tumour evolution

Bailey, C; Shoura, MJ; Mischel, PS; Swanton, C; (2020) Extrachromosomal DNA d relieving heredity constraints, accelerating tumour evolution. Annals of Oncology , 31 (7) pp. 884-893. 10.1016/j.annonc.2020.03.303. Green open access

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Abstract

Oncogene amplification on extrachromosomal DNA (ecDNA) provides a mechanism by which cancer cells can rapidly adapt to changes in the tumour microenvironment. These circular structures contain oncogenes and their regulatory elements, and, lacking centromeres, they are subject to unequal segregation during mitosis. This non-Mendelian mechanism of inheritance results in increased tumour heterogeneity with daughter cells that can contain increasingly amplified oncogene copy number. These structures also contain favourable epigenetic modifications including transcriptionally active chromatin, further fuelling positive selection. ecDNA drives aggressive tumour behaviour, is related to poorer survival outcomes and provides mechanisms of drug resistance. Recent evidence suggests one in four solid tumours contain cells with ecDNA structures. The concept of tumour evolution is one in which cancer cells compete to survive in a diverse tumour microenvironment under the Darwinian principles of variation and fitness heritability. Unconstrained by conventional segregation constraints, ecDNA can accelerate intratumoral heterogeneity and cellular fitness. In this review, we highlight some of the recent discoveries underpinning this process.

Type: Article
Title: Extrachromosomal DNA d relieving heredity constraints, accelerating tumour evolution
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.annonc.2020.03.303
Publisher version: https://doi.org/10.1016/j.annonc.2020.03.303
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Oncology, HOMOGENEOUSLY STAINING REGIONS, DOUBLE MINUTE CHROMOSOMES, DIHYDROFOLATE-REDUCTASE GENE, EPSTEIN-BARR-VIRUS, CIRCULAR DNA, C-MYC, AMPLIFICATION, RESISTANCE, REPLICATION, ORIGIN
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10107641
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