The Clonal Evolution of Tumor Cell Populations: Acquired genetic lability permits stepwise selection of variant sublines and underlies tumor progression.

PC Nowell - Science, 1976 - science.org
PC Nowell
Science, 1976science.org
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 instability and associated selection process, most readily …
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 instability 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.
AAAS