Traditionally, it is thought that malignancy occurs when a single cell is able to acquire all the necessary mutations required. This project aims to challenge this theory, by showing that two or more clones containing distinct mutations are capable of cooperating with one another to form a malignancy.
We will take two approaches to test this theory. Firstly, we will use ultraviolet light to induce skin tumors in transgenic mice that express multiple fluorescent proteins. We will monitor the clonal composition by fluorescent microscopy during the formation and progression of these tumours. Should the tumours that arise be multiclonal, they will then be injected back into genetically identical mice, to ultimately test interclonal co-operativity. Preliminary data obtained by our lab has shown that non-tumorigenic cells that are mutated to be highly proliferative can cooperate with cells of the same origin that undergo epithelial-mesenchymal-transitions, to become both tumorigenic and metastatic. This information will allow for more specific therapies to be designed, dependent on the clonality of tumours, the mutations present and the pathways activated, resulting in better efficacy.