Modifiers of mammary tumor progression and metastasis on mouse chromosomes 7, 9, and 17.

Tumor progression, the growth and dissemination of primary tumor to secondary sites, is of critical clinical importance since the vast majority of patients succumb to metastatic disease rather than to the primary tumor. Many factors are likely to influence this process, including the primary oncogenic events, environmental exposures and stress and progressive stochastic mutations. Previously, our laboratory demonstrated that an additional factor, the genetic background on which tumors arose, had a significant effect on metastatic efficiency. Using a highly metastatic transgene-induced mammary tumor model, a locus modulating metastatic efficiency, Mtes1, was localized on proximal mouse Chromosome 19. In addition, a number of additional suggestive loci were observed on several other chromosomes. To confirm the presence of these additional loci before initiating cloning strategies, chromosomal substitution strains have been constructed and assayed for modification of the cancer phenotypes. Using the chromosomal substitution strains, an additional modifier modulating tumor latency was confirmed, as well as three new modifier genes that alter the kinetics of tumor progression. Identification and analysis of these loci will likely present interesting and novel information about cancer heterogeneity in the human population.