How tumors arise from individual transformed cells within an intact epithelium is a central, yet unanswered question. Here, we developed a new methodology that combines breast tissue organoids, where oncogenes can be switched on in single cells, with light-sheet imaging that allows us to track cell fates using a big-image-data analysis workflow. The power of this integrated approach is illustrated by our finding that small local groups of transformed cells form tumors while isolated transformed cells do not.

Tracking the cells of tumor origin in breast organoids by light sheet microscopy