Extrachromosomal DNA (ecDNA) in Cancer

Learn about extrachromosomal DNA (ecDNA), circular or linear DNA segments found outside chromosomes. Explore their roles in cancer, gene amplification, and genetic evolution across various organisms.

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Scientists have discovered a weakness in cancer cells with ecDNA. By targeting a specific protein (CHK1) involved in DNA repair, they can selectively kill these cancer cells. This could lead to new, more effective treatments for certain types of cancer.

Extrachromosomal DNA (ecDNA)

ecDNA are small circular DNA fragments that float freely in the nucleus, separate from chromosomes.
Genesis: Formed due to DNA damage (e.g., chromothripsis) or errors during DNA replication.
Role of ecDNA in Cancer:
- Found in up to 90% of certain tumour types, including brain tumours, liposarcomas, and breast cancers.
- ecDNA often contains multiple oncogenes, promoting tumour growth and drug resistance.
  - Oncogenes are mutated genes capable of causing cancer that are required to activate tumour growth.

Why is ecDNA a problem?

Cancer Growth: ecDNA can carry multiple copies of cancer-causing genes, making tumors grow faster and become more aggressive.
Drug Resistance: Cancer cells with ecDNA can evolve more quickly, making them resistant to treatments.

Extrachromosomal DNA (ecDNA) in Cancer

Extrachromosomal DNA (ecDNA) plays a significant role in cancer biology due to its unique properties and functions:

Key Roles of ecDNA in Cancer

Gene Amplification: ecDNA often carries oncogenes, such as MYC or EGFR, enabling their amplification beyond chromosomal control. This overexpression drives tumor growth and malignancy.
Heterogeneity and Evolution: ecDNA replicates independently, contributing to genetic variability within tumors. This dynamic nature allows tumors to adapt rapidly to environmental pressures, such as drug treatments.
Resistance to Therapy: Cancer cells with ecDNA can exhibit resistance to chemotherapy and targeted treatments due to amplified drug-resistance genes or adaptive mutations.
Increased Oncogenic Potential: ecDNA lacks the regulatory constraints of chromosomal DNA, resulting in the unregulated activity of genes that promote cell proliferation and survival.
Biomarker Potential: The detection of ecDNA in circulating tumor DNA offers promise as a diagnostic tool for identifying cancers and monitoring treatment response.

Clinical and Research Implications

Diagnostics: Liquid biopsy techniques are being developed to detect ecDNA as a non-invasive cancer diagnostic marker.
Therapeutics: Strategies targeting ecDNA replication or stability are under exploration to combat drug resistance and tumor progression.