ecDNA
Context
Recently, a research team led by the eDyNAmiC revealed groundbreaking insights into extrachromosomal DNA (ecDNA) that challenge the traditional principle of genetics and underscore the role of ecDNA in cancer growth.
Relevance:
GS-03 (Science and technology)
Dimensions of the Article
- About the New Study
- About ecDNA
- Significance of the Study
About the New Study
- Key Findings
- On the observations made on approximately 15,000 cancer samples of the U.K.’s 100,000 Genomes Project, covering 39 tumour types, it was found that ecDNA was present in about 17% of tumours and was especially prevalent in liposarcomas, brain tumours, and breast cancers.
- It was also found that the EcDNA frequency increased after treatments like chemotherapy, correlating with metastasis and poorer patient outcomes.
- Single-cell sequencing reveals how ecDNA interacts with other DNA fragments to amplify oncogenes.
- The fluorescence in-situ hybridisation (FISH) method validated findings by detecting cancer-specific genes in the relevant tissue samples.
About ecDNA
- What is ecDNA?
- EcDNA are small fragments that break away from the chromosomes and float freely in the nucleus. They often arise due to errors in DNA replication or structural damage, such as chromothripsis, where chromosomes break and rearrange.
- Role in Cancer:
- EcDNA contains amplified oncogenes, which are responsible for tumour growth. Unlike chromosomal DNA, ecDNA moves freely, forming hubs that intensify oncogene expression.
- This dynamic leads to accelerated tumour evolution and drug resistance.
- Genetic Implications:
- The study challenges Mendel’s third law of independent assortment.
- Unlike chromosomal genes, ecDNA clusters are inherited together during cell division, preserving cancer-favouring genetic combinations in daughter cells.
Significance of the Study
- Challenging Traditional Genetics: ecDNA demonstrates coordinated segregation, giving cancer cells an adaptive edge. This new study has overturned the age-old belief that non-linked genes are inherited randomly.
- New Vulnerabilities: It is clear from the findings that EcDNA-dependent tumours rely heavily on the CHK1 protein to manage DNA repair during rapid growth. This makes it obvious to block CHK1 with drugs like BBI-2779 selectively that can kill ecDNA-driven cancer cells, reducing tumour size significantly.
- Impact on Cancer Treatment: EcDNA-driven cancers such as glioblastoma, ovarian, and lung cancers are notoriously resistant to current treatments. This study opens avenues for targeted therapies.
Way Forward
- More studies are needed to understand how ecDNA forms and interacts with the genetic environment.
- Raising awareness about ecDNA’s role in cancer can drive innovation and funding for therapeutic development.
- These findings have the potential to transform cancer biology, offering hope for more effective treatments and challenging long-standing genetic principles.
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