Context
An international collaboration by a team called eDyNAmiCled has discovered how ecDNA contributes to the progression of cancer and drug resistance.
About Extrachromosomal DNA (ecDNA):
- ecDNA refers to small fragments of genetic material found in cancer cells.
- ecDNA is present in up to 40% of cancer cell lines and 90% of brain tumour samples.
- Formation of ecDNA
- ecDNA forms when a part of DNA breaks away from chromosomes and forms a circular structure.
- This process occurs due to DNA damage like chromothripsis or copying errors during cell division.
- Genetic Findings
- Oncogenes, mutated genes that cause cancer, often reside in ecDNA, not in chromosomes.
- ecDNA is not fixed in specific locations, unlike chromosomal DNA, and can interact with other ecDNA, forming hubs.
- When ecDNA is transcribed to mRNA, certain oncogenes become four times more prevalent, enhancing tumour growth.
- New Genetic Insights
- Mendel’s third law of independent assortment states that genes on different chromosomes segregate randomly during cell division.
- However, ecDNA violates this law, clustering together during cell division, which provides cancer cells with an advantage. This is called the “jackpot effect”.
- Impact on Cancer Evolution & Drug Resistance
- ecDNA contributes to tumour evolution, drug resistance, and metastasis.
- Presence of ecDNA in tumour cells may lead to worse patient outcomes after treatments like chemotherapy.
- Vulnerabilities in Tumours with ecDNA
- ecDNA increases the activity of specific genes, which can lead to DNA damage.
- Cells use the protein CHK1 to repair DNA and continue growing.
- Blocking CHK1 with a drug called BBI-2779 has been shown to selectively kill cancer cells with ecDNA, reducing tumours in mice.
- Therapeutic Implications
- Boundless Bio, a biotech company, is working to target ecDNA vulnerabilities in cancers like glioblastoma, ovarian, and lung cancers.
- These findings may lead to new treatment options for cancers driven by ecDNA.
Source: TH
Previous Year Question
‘Microsatellite DNA’ is used in the case of which one of the following?
[UPSC Civil Services Exam – 2023 Prelims]
(a) Studying the evolutionary relationships among various species of fauna
(b) Stimulating ‘stem cells’ to transform into diverse functional tissues
(c) Promoting clonal propagation of horticultural plants
(d) Assessing the efficacy of drugs by conducting series of drug trials in a population
Answer: (a)
