Metastatic Potential: Generic Predisposition of the Primary Tumor or Rare, Metastatic Variants—Or Both?

Metastasis is a rare event. Does it arise from rare, variant, highly metastatic cells or does a primary tumor progress to a premalignant state from which metastases arise stochastically without further changes in gene expression? Arguments and evidence have been adduced to support either position. A paper in this monthʹs Cancer Cell and other arguments instead suggest models combining features of both.