The met oncogene drives a genetic program linking cancer to hemostasis

To study the early events of transformation in a setting that recapitulates the natural occurrence of sporadic cancer, it would be ideal to develop a model that initiates from single somatic cells harbouring mutations of one or more cancer-related genes, but intermingled with their normal tissue context. We have set up a mouse model of somatic oncogene delivery, relying on the unique properties of late-generation lentiviral vectors1 (LV). LV enable oncogene targeting by non-viral promoters in post-natal life, and transformation of somatic cells that remain functionally interlocked within the normal tissue. Through LV, we targeted the activated MET oncogene to the mouse liver. We detected development of foci of hepatocyte clonal expansion, which slowly progressed towards malignancy.