Molecular_analysis_of_p53_mutant_epidermis

The sun-exposed epidermis of middle -aged humans contains a high burden of clones carrying oncogenic driver mutaions, but how they form and their effects on tissue are unclear. We set up the conditional mouse model system which express a p53 mutant common in human skin squamous cell carcinoma. Wild tyoe progenitors generated equal propotions of progenitor and differentiating daughters on average, whereasp53 mutant cells produced an excess of mutant progenitors. As a result, mutant clones progressively spread through the epidermis, a process accelerated by low doses of UV light. However, over the months following colonisation the tissue establish a new steady state.We conclude p53mtation inhibits progenitor cell differneriation and drives clonal expansion but it then constrained enabling the epidermis to tolerate a high burden of mutant cells. Molecular mechanism of p53 mutant keratinocyte behaviour to be elucidated.