Metastatic variants are generated spontaneously at a high rate in mouse KHT tumor.

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Abstract
The Luria-Delbruck fluctuation analysis was used to examine the lung tumor-forming ability of a series of parallel clones derived from the KHT [mouse sarcoma] tumor, grown to small defined sizes. Metastatic variants arise spontaneously in the clonal lines during their growth, at an apparent rate of .apprxeq. 10-5 per cell per generation. This rapid rate has implications for understanding tumor heterogeneity and the process of tumor progression. Previous results have suggested that heterogeneity observed in cloning experiments reflects stable subpopulations of cells in the original tumor. An alternative dynamic heterogeneity model is proposed, in which metastatic variants arise at a high rate (as detected in the cloning experiments) but need not be stable mutations in order to effectively produce metastases.