The Intersection of Inheritance and Metastasis: the Role and Implications of Germline Polymorphism in Tumor Dissemination

Metastasis is an enormously complex process that involves both spatial and temporal barriers. Metastatic cells must not only acquire all of the characteristics of a primary tumor, but additionally must be capable of invasion, survival during transit and in the secondary site, interact productively with a novel microenvironment and proliferate to form a clinically relevant lesion.(1) Adding complexity to the process is the fact that it can be years or even decades after diagnosis of the primary tumor before the secondary tumors are apparent. A number of models have been proposed to explain the origins of metastasis. However, while all of the models can account for some aspects of the experimental observations, suggesting they may be at least in part true, none adequately explain all of the data. This implies that the existing models are likely to be too simplistic and additional factors must be considered to adequately account for existing and newly emerging data.