Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution

DOI Web Site Web Site 被引用文献7件
  • Shaoping Ling
    Key Laboratory of Genomics and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
  • Zheng Hu
    Key Laboratory of Genomics and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
  • Zuyu Yang
    Key Laboratory of Genomics and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
  • Fang Yang
    Key Laboratory of Genomics and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
  • Yawei Li
    Key Laboratory of Genomics and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
  • Pei Lin
    State Key Laboratory of Biocontrol, College of Ecology and Evolution, Sun Yat-Sen University, Guangzhou 510275, People’s Republic of China;
  • Ke Chen
    Key Laboratory of Genomics and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
  • Lili Dong
    Key Laboratory of Genomics and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
  • Lihua Cao
    Key Laboratory of Genomics and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
  • Yong Tao
    Key Laboratory of Genomics and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
  • Lingtong Hao
    Key Laboratory of Genomics and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
  • Qingjian Chen
    State Key Laboratory of Biocontrol, College of Ecology and Evolution, Sun Yat-Sen University, Guangzhou 510275, People’s Republic of China;
  • Qiang Gong
    Key Laboratory of Genomics and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
  • Dafei Wu
    Key Laboratory of Genomics and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
  • Wenjie Li
    Key Laboratory of Genomics and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
  • Wenming Zhao
    Key Laboratory of Genomics and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
  • Xiuyun Tian
    Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital, Beijing 100142, People's Republic of China;
  • Chunyi Hao
    Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital, Beijing 100142, People's Republic of China;
  • Eric A. Hungate
    Department of Pediatrics, University of Chicago, Chicago, IL 60637;
  • Daniel V. T. Catenacci
    Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637;
  • Richard R. Hudson
    Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637;
  • Wen-Hsiung Li
    Biodiversity Research Center, Academia Sinica, Taipei 11529, Taiwan
  • Xuemei Lu
    Key Laboratory of Genomics and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
  • Chung-I Wu
    Key Laboratory of Genomics and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing 100101, People's Republic of China;

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<jats:title>Significance</jats:title> <jats:p>A tumor comprising many cells can be compared to a natural population with many individuals. The amount of genetic diversity reflects how it has evolved and can influence its future evolution. We evaluated a single tumor by sequencing or genotyping nearly 300 regions from the tumor. When the data were analyzed by modern population genetic theory, we estimated more than 100 million coding region mutations in this unexceptional tumor. The extreme genetic diversity implies evolution under the non-Darwinian mode. In contrast, under the prevailing view of Darwinian selection, the genetic diversity would be orders of magnitude lower. Because genetic diversity accrues rapidly, a high probability of drug resistance should be heeded, even in the treatment of microscopic tumors.</jats:p>

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