Context:
Previously ignored, extrachromosomal DNA (ecDNA) is now taking centre-stage in the complex field of cancer biology.
What is ecDNA?
- Extrachromosomal DNA or ecDNA is a breakaway fragment from chromosomes that floats freely in the cell nucleus.
- ecDNA is formed when mistakes occur during cell replication.
New findings on ecDNA
- Prevalence in cancer cells: A 2017 study revealed ecDNA is present in nearly 40% of cancer cell lines and in up to 90% of patient-derived brain tumour samples.
- Factors for eDNA formation: Environmental factors like smoking and exposure to certain substances can trigger DNA damage and lead to ecDNA formation.
- Concentration of oncogenes: ecDNA contains oncogenes – mutated genes capable of causing cancer. Since ecDNA moves freely, it interacts with other ecDNA to form hubs where oncogenes are concentrated.
- Fighting cancer cells: Researchers found that a drug, BBI-2779, kills cancer cells with ecDNA by blocking CHK1, a protein that is activated by cancer cells. This has promise for patients with ecDNA-driven cancers, such as glioblastoma and ovarian and lung cancers.
Challenge to Mendel’s third law
- When cells divide, they duplicate chromosomes and equally distribute them among daughter cells. Genes on the same chromosome are inherited together, while those on different chromosomes segregate independently. This genetic principle is known as Mendel’s third law of independent assortment (named after Gregor Mendel).
- The researchers found that, contrary to the law, ecDNA is passed on in clusters to the daughter cells during cell division. This allows them to enhance gene interactions, support cancer growth, and preserve favourable genetic combinations over multiple life-cycles. The researchers have called this the “jackpot effect”.
- This refutes the idea that gene inheritance is entirely random when the genes are not linked by DNA strands.