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Updated: Mar 7, 2026

Author Spotlight: FISH as a Tool for Precise Gene Amplification Assessment in Cancer Specimens
Published on: July 12, 2024
Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity
Kristen M Turner1, Viraj Deshpande2, Doruk Beyter2
1Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, California 92093, USA.
Extrachromosomal DNA (ecDNA) is found in nearly half of human cancers, unlike normal cells. This circular DNA amplifies oncogenes, accelerating cancer evolution and increasing intratumoural heterogeneity.
Area of Science:
- Genomics
- Cancer Biology
- Molecular Genetics
Background:
- Human cells possess 23 pairs of chromosomes.
- Gene amplification in cancer can occur on chromosomes or extrachromosomal DNA (ecDNA).
- The prevalence and functional significance of ecDNA in cancer remain largely unknown.
Purpose of the Study:
- To investigate the frequency and functional importance of ecDNA in human cancers.
- To develop a method for unbiased ecDNA detection and analysis.
- To understand the role of ecDNA in cancer evolution.
Main Methods:
- Whole-genome sequencing and cytogenetic analyses of 2,572 dividing cells from 17 cancer types.
- Structural modeling of chromosomal and extrachromosomal DNA.
- Development of the ECdetect software package for integrated ecDNA analysis.
Main Results:
- ecDNA was detected in nearly 50% of human cancers, with varying frequencies across tumour types.
- ecDNA was rarely observed in normal cells.
- Driver oncogenes were frequently amplified on ecDNA, leading to increased transcript levels.
- Mathematical modeling and quantitative analyses confirmed that ecDNA amplification enhances oncogene copy number and intratumoural heterogeneity more effectively than chromosomal amplification.
Conclusions:
- ecDNA is a common feature in human cancers, significantly contributing to oncogene amplification.
- ecDNA plays a crucial role in accelerating cancer evolution and increasing intratumoural heterogeneity.
- The findings highlight ecDNA as a potential target for cancer therapy.
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