Oncogenic Mutations and Clonal Expansion in Tumour Development

However, the ways in which oncogenic mutations affect the balance between renewal and differentiation and lead to clonal expansion , cell competition , tissue colonization and tumour development are unknown.

Here, through multidisciplinary approaches that combine in vivo clonal analysis using intravital microscopy, single-cell analysis and functional analysis, we show how SmoM2—a constitutively active oncogenic mutant version of Smoothened (SMO) that induces the development of basal cell carcinoma—affects clonal competition and tumour initiation in real time. We found that expressing SmoM2 in the ear epidermis of mice induced clonal expansion together with tumour initiation and invasion. By contrast, expressing SmoM2 in the back-skin epidermis led to a clonal expansion that induced lateral cell competition without dermal invasion and tumour formation. Single-cell analysis showed that oncogene expression was associated with a cellular reprogramming of adult interfollicular cells into an embryonic hair follicle progenitor (EHFP) state in the ear but not in the back ski

Oncogenic Mutations Clonal Expansion Cell Competition Tissue Colonization Tumour Development Constitutively Active Oncogenic Mutant Smom2 Basal Cell Carcinoma Intravital Microscopy Single-Cell Analysis Functional Analysis Ear Epidermis Back-Skin Epidermis Cellular Reprogramming Embryonic Hair Follicle Progenitor

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