Tumor cell genetic diversity is much larger than expected
November 20, 2015 Source: Xinhuanet
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];Why is the tumor difficult to cure? A study by the Beijing Institute of Genomics of the Chinese Academy of Sciences and the University of Chicago showed that the number of genetic variations in tumors is much higher than traditional expectations, probably because tumor cell evolution does not fully follow Darwin's evolutionary theory. This massive genetic variation makes tumor cells susceptible to drug resistance and rapid metastasis. This achievement was published online in the Proceedings of the National Academy of Sciences.
Studies have shown that tumorigenesis is a process of somatic cell evolution, just like natural population diversity, a process of random mutation and natural selection. The Darwinian evolutionary theory of cancer suggests that a small number of tumor cells may undergo certain mutations, giving them a growth advantage. Over time, this cell becomes the "main body" of the tumor. However, this view may underestimate the genetic diversity within the tumor, thereby underestimating the probability that the tumor will become resistant to the drug, and will not fully explain why the tumor is highly metastatic.
The research team led by Wu Zhongyi and Lu Xuemei, researchers at the Beijing Institute of Genomics of the Chinese Academy of Sciences, cut nearly 300 samples from a liver cancer section and performed gene sequencing and data analysis with nearly 2000-fold coverage. Estimated by a neutral model, a tumor with a diameter of about 3.5 cm carries hundreds of millions of mutations, thousands of times higher than previously estimated. Wu Zhongyi said: "Because of so many mutations, even with active treatment, the probability of tumor clones with specific mutations surviving is high, and these cells can proliferate to form new drug-resistant tumor clones."
The guiding significance of this study for the clinical treatment strategy of tumors is that a high degree of genetic heterogeneity indicates a high probability of resistance mutations in the tumor cell population. In order to rapidly remove tumor cells, a highly destructive treatment strategy is usually used, which may not only fail, but even promote the expansion and development of resistant clones because the main clones are inactivated.
But the researchers also cautioned that the study did not completely deny the role of Darwin's selection at the cellular level. "The non-Darwin process may not accurately characterize the genetic heterogeneity between different tumors (same or different organs), or The process of non-tumor to tumor evolution". The in-depth analysis of different types of tumors and their anti-drug or relapse processes will help scientists to fully understand the commonality and individual specificity of tumor development and development, and consider and study individualized treatment strategies.
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