Division of Hematology & Hemostaseology, Medical University of Vienna, Vienna, Austria.
Cancer Res. 2013 Feb 1;73(3):1037-45. doi: 10.1158/0008-5472.CAN-12-3678. Epub 2013 Jan 23.
Accumulating evidence suggests that human cancers develop through a step-wise, but nonlinear process of cellular diversification and evolution. Recent mutational analyses indicate that this process is more complex and diverse than anticipated before whole-genome sequencing methods were readily available. Examples are also emerging now of genetically abnormal clones of cells that have acquired mutations with known oncogenic potential but, nevertheless, may show no manifestations of malignant change for many years. To accommodate these diverse realities, we suggest the term neoplastic refer to clones of cells that have any type of somatic aberrancy associated with an increased propensity to become malignant, and the derivative term neoplastic stem cell be adopted to identify the cells responsible for the long-term maintenance of such clones. Neoplastic clones would thus include those that never evolve further, as well as those that eventually give rise to fully malignant populations, and all stages in between. The term cancer stem cells would then be more appropriately restricted to cells generating subclones that have established malignant properties. More precise molecular understanding of the different stem cell states thus distinguished should contribute to the development of more effective prognostic and therapeutic tools for cancer diagnosis and treatment.
越来越多的证据表明，人类癌症是通过细胞多样化和进化的逐步但非线性过程发展而来的。最近的突变分析表明，在全基因组测序方法广泛应用之前，这一过程比预期的更为复杂和多样化。现在也有越来越多的例子表明，具有已知致癌潜力的基因突变的细胞遗传异常克隆，尽管如此，可能在多年内没有表现出恶性变化的迹象。为了适应这些多样化的现实，我们建议使用术语“肿瘤性”来指代具有任何类型与恶性倾向增加相关的体细胞异常的细胞克隆，采用衍生术语“肿瘤性干细胞”来识别负责长期维持此类克隆的细胞。肿瘤性克隆将包括那些从未进一步进化的克隆，以及那些最终导致完全恶性群体的克隆，以及两者之间的所有阶段。“癌症干细胞”这一术语将更适当地限制在产生已建立恶性特性的亚克隆的细胞上。因此，对不同干细胞状态的更精确的分子理解应该有助于开发更有效的癌症诊断和治疗的预后和治疗工具。
