Nowell P C
Science. 1976 Oct 1;194(4260):23-8. doi: 10.1126/science.959840.
It is proposed that most neoplasms arise from a single cell of origin, and tumor progression results from acquired genetic variability within the original clone allowing sequential selection of more aggressive sublines. Tumor cell populations are apparently more genetically unstable than normal cells, perhaps from activation of specific gene loci in the neoplasm, continued presence of carcinogen, or even nutritional deficiencies within the tumor. The acquired genetic insta0ility and associated selection process, most readily recognized cytogenetically, results in advanced human malignancies being highly individual karyotypically and biologically. Hence, each patient's cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline resistant to the treatment. More research should be directed toward understanding and controlling the evolutionary process in tumors before it reaches the late stage usually seen in clinical cancer.
有人提出，大多数肿瘤起源于单个细胞，肿瘤进展是由于原始克隆内获得的遗传变异性，从而允许依次选择更具侵袭性的亚系。肿瘤细胞群体在遗传上显然比正常细胞更不稳定，这可能是由于肿瘤中特定基因位点的激活、致癌物的持续存在，甚至是肿瘤内的营养缺乏。获得性遗传不稳定性和相关的选择过程，最容易通过细胞遗传学识别，导致晚期人类恶性肿瘤在核型和生物学上具有高度个体性。因此，每个患者的癌症可能需要个体化的特异性治疗，甚至这可能会因出现对治疗耐药的遗传变异亚系而受阻。在肿瘤进化过程达到临床癌症中常见的晚期之前，应该进行更多的研究来理解和控制肿瘤的进化过程。
