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

Abstract:

:Using the Luria-Delbrück fluctuation analysis, we have examined the lung tumor-forming ability of a series of parallel clones derived from the KHT tumor, grown to small defined sizes. From these studies, we conclude that metastatic variants arise spontaneously in the clonal lines during their growth, at an apparent rate of approximately 10(-5) per cell per generation. This rapid rate has implications for our understanding of 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. We propose here an alternative "dynamic heterogeneity" model, 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.

authors

Harris JF,Chambers AF,Hill RP,Ling V

doi

10.1073/pnas.79.18.5547

subject

Has Abstract

pub_date

1982-09-01 00:00:00

pages

5547-51

issue

18

eissn

0027-8424

issn

1091-6490

journal_volume

79

pub_type

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