肿瘤遗传异质性

Tumor genetic heterogeneity

尽管大多数自发性肿瘤源于单细胞,但人们逐渐认识到个体肿瘤的内部存在异质性,这种差异涉及分化程度、细胞增殖率、侵袭和转移能力及治疗反应等众多方面。分子生物学研究也证实肿瘤演进过程中不断产生新的突变,为肿瘤内部存在异质性增加了更有力的佐证。文章综述了关于肿瘤遗传异质性研究的主要进展。鉴于遗传异质性分析可为揭示肿瘤细胞的产生、扩散、转移的时间段提供重要信息,文章以瘤内异质性为主线,列举了遗传异质性存在的实验依据;阐述了遗传多样性在人类个体肿瘤发展进化史中的研究价值;介绍了遗传异质性产生的两种模式,包括肿瘤干细胞模型和克隆进化模型;总结了遗传异质性在肿瘤转移、治疗中的重要临床意义。文章最后展示了常用的遗传异质性的研究方法,包括特定基因的分析方法和基于基因组水平的方法,并对各自的优缺点进行了分析。

Although the majority of spontaneous tumors derive from a single cell, people have come to realize intra-tumor heterogeneity of individual tumors. Human cancers frequently display substantial difference in phenotypic features, such as the degree of differentiation, cell proliferation rate, invasion and metastatic potential, response to therapy and many other aspects. Molecular biology studies have confirmed the occurrence of new mutations during the process of tumor progression, which provide more powerful evidences to show the existence of intra-tumor genetic heterogeneity. This review will focus on recent major advances in the study of tumor genetic heterogeneity. Considering that genetic heterogeneity analysis can provide important information to indicate how long normal cells transform into tumor cells and how to spread and migrate, we firstly describe experimental evidences of intra-tumor genetic heterogeneity. Then we discuss the research value of genetic diversity in the evolutionary history of human individual tumor, introduce the two modes of the genetic heterogeneity -- cancer stem cell model and the clonal evolution model, and summarize the implications of intra-tumor heterogeneity studies in metastasis and therapy. In addition, the article presents the research methods of genetic heterogeneity, including specific gene and genome-wide level, pointing out their strengths and limitations.