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Author Spotlight: FISH as a Tool for Precise Gene Amplification Assessment in Cancer Specimens
Published on: July 12, 2024
Extrachromosomal DNA: An Emerging Hallmark in Human Cancer
Sihan Wu1, Vineet Bafna2, Howard Y Chang3
1Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas, USA;
Abstract:
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.
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