Extrachromosomal DNA: An Emerging Hallmark in Human Cancer

Human genes are arranged on 23 pairs of chromosomes, but in cancer, tumor-promoting genes and regulatory elements can free themselves from chromosomes and relocate to circular, extrachromosomal pieces of DNA (ecDNA). ecDNA, because of its nonchromosomal inheritance, drives high-copy-number oncogene...

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Bibliographic Details
Published inAnnual review of pathology Vol. 17; p. 367
Main Authors Wu, Sihan, Bafna, Vineet, Chang, Howard Y, Mischel, Paul S
Format Journal Article
LanguageEnglish
Published United States 24.01.2022
Subjects
DNA - genetics
Humans
Neoplasms - genetics
Neoplasms - pathology
Oncogenes
cancer genomics
extrachromosomal DNA
tumor evolution
non-Mendelian inheritance
ecDNA
gene amplification
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Summary:Human genes are arranged on 23 pairs of chromosomes, but in cancer, tumor-promoting genes and regulatory elements can free themselves from chromosomes and relocate to circular, extrachromosomal pieces of DNA (ecDNA). ecDNA, because of its nonchromosomal inheritance, drives high-copy-number oncogene amplification and enables tumors to evolve their genomes rapidly. Furthermore, the circular ecDNA architecture fundamentally alters gene regulation and transcription, and the higher-order organization of ecDNA contributes to tumor pathogenesis. Consequently, patients whose cancers harbor ecDNA have significantly shorter survival. Although ecDNA was first observed more than 50 years ago, its critical importance has only recently come to light. In this review, we discuss the current state of understanding of how ecDNAs form and function as well as how they contribute to drug resistance and accelerated cancer evolution.
ISSN:1553-4014
DOI:10.1146/annurev-pathmechdis-051821-114223