The use of quantitative genetics for estimating the non-inherited and inherited contributions to metastasis formation.

The contribution of both non-inherited (stochastic, random, environmental, and other non-inherited influences) and inherited factors (genetic and inherited epigenetic factors) to the variability of spontaneous lung metastasis formation in over 100 metastatic lines from each of three murine tumors was measured. The contribution of inherited and genetic sources of variability to metastasis formation was significantly greater than 0 in all cases, but only in the lines of sarcoma SANH was it the major influence on metastatic variability. In the sarcoma SA4020 and hepatocarcinoma HCA-1 lines, non-inherited factors accounted for the majority of the variation in spontaneous lung metastasis formation. A similar situation was also observed in the variability of the tumors with respect to the diameter doubling time. In conclusion, both non-inherited and genetic/inherited factors significantly influenced the formation of spontaneous metastases in the tumors examined. The significance of this finding for the cloning of metastatic genes is discussed.