MYC ectopic expression establishes a precancerous field leading to multifocal lesions in a Drosophila epithelial model

The term “field cancerisation” describes a precancerous area in which genetically altered but histologically normal tissues proceed towards the development of multiple malignant foci. In the early stages of tumour progression cells may indeed acquire genetic damages that allow them to proliferate in patches of altered cells gradually replacing normal tissue. This mechanism invokes MYC-mediated cell competition (MMCC), a phenomenon characterised in Drosophila consisting in fitness confrontation between cells sharing the same tissue, with cells expressing high MYC levels ultimately killing and replacing cells showing lower MYC activity. These intrinsic features of MMCC make it a candidate mechanism pioneering field cancerisation. Here we mimic field formation by upregulating MYC in a territory of the larval wing epithelium of Drosophila. Analysis of specific markers usually found in mammalian precancerous areas confirmed that MYC upregulation is sufficient to trigger specific cellular responses. Moreover, MYC-expressing fields were susceptible to the development of multifocal tumours upon induction of different second mutations, a typical trait correlated to mammalian field cancerisation. In summary, our study identified an undescribed early genetic change implicated in field cancerisation and established a genetically amenable model which may help study the molecular basis of the initial tumourigenic events.