Fig. 2

A depiction of the growth patterns of terminally benign papillomas (a) and an example of those that progress to become invasive carcinomas (b), followed by spreading beyond the tumor margins to distant sites (Metastasis). Colors represent groups of cells that have arisen from one original colored cell (clones). a The major blue color represents the original clone that arose from the first initiated cell, and subsequently gave rise to the broad yellow, red and green clones during papilloma growth. Papillomas also incorporate normal clones of cells (streaks) that are mainly at the periphery of the tumor (thin red and green clones). The new papilloma clones do not generally intermix inter- mix, and only one will progress to malignancy. b Progression to malignancy and metastasis. At the benign-malignant transition, a clonal sweep results in the emergence of a single red dominant clone, but this is followed by generation of new clones that show evidence of intermixing. This property has only been seen thus far in malignant tumors. Two or more of these intermixing clones can cooperate to drive growth and metastasis