Nature Genetics: Is the weapon of cancer "evolution"? Scientists have found that cancer genes amplification in chromosome DNA can promote tumor development.

Chromosomal extrachromosomal DNA (ecDNA), a dna that falls off stable genomic DNA and exists in a single or double-stranded ring, promotes the expression of cancer genes in tumor cells.
addition, the primary cancer genes on ecDNA make tumor cells more adaptable to the environment and respond to changes in the tumor's internal environment.
previous studies have speculated that cancer-inducing is essentially an "evolutionary" manifestation.
ecDNA will change the expression of cancer genes that drive cancer, and the cancer genes and the regulatory regions around them are free of chromosomal constraints, thus promoting tumor growth and playing a key role in tumor resistance.
recently, a team of researchers at the University of California, San Diego, published an article in nature Genetics called "Extrachromosomal DNA is associated with withcogene amplification and poor outcomes and multiple cancers", revealing for the first time the presence of ecDNA amplification in multiple cancers.
, at least 14 percent of tumors have ecDNA, and ecDNA amplification in other malignancies is more frequent.
therefore, targeting ecDNA to interfere with tumor growth, treat drug resistance and prevent recurrence is a promising direction for treating cancer.
Doi:10.1038/s41588-020-0678-2 In this study, researchers examined the frequency of ecDNA amplification by analyzing genome-wide sequencing data from 3,212 cancer patients.
results show that ecDNA amplification often occurs in multiple cancers, rather than in blood or normal tissues.
this means that cancer genes are mainly found in amplified ecDNA, including the most common relapsed cancer genes, which lead to higher levels of cancer gene transcription, which accelerates cancer progression.
note that ecDNA-based cyclic amplifications were observed in all 25 cancer types.
even in the most invasive cancers, such as glioblastoma, sarcoma and esophageal cancer, high-frequency ring-shaped ecDNA amplifications occur.
the frequency of cyclic amplification across tumors and non-tumor tissues (partial screenshots), the researchers analyzed transcription results of ring ecDNA amplification.
, as expected, they found that DNA copy numbers (DNA-CN) were highly associated with the level of expression of cancer genes in all amplification subcategories.
means that the amplification of ring ecDNA may be the underlying cause of tumor heterogeneity, which in simple terms promotes tumor growth and invasion.
gene expression of the ecDNA amplification group To further study whether the cancer in which ecDNA amplification occurs is associated with invasive biological characteristics, the researchers examined the effects of ecDNA amplification on lymph nodes.
found that the amplification of ecDNA was associated with tumor invasiveness.
addition, the five-year survival rate of tumor patients with ecDNA amplification was significantly worse than in patients with non-amplified tumors.
Adverse effects of circulatory amplification, the study found that cyclic ecDNA played a key role in the development and development of cancer, not only promoting the "compression" of DNA and transcription of cancer genes, but also adversely affecting the likely course and outcome of cancer patients.
Of course, if we can find a gene in ecDNA that is directly related to cancer, we can not only use ecDNA amplification as a cancer detection marker, but also use targeted ecDNA to interfere with tumor growth, treat drug resistance and prevent recurrence.
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