Driver mutations in cancer genome of Nothobranchius furzeri: from tumor biology to concept of experimental model of spontaneous carcinogenesis

African annual killifish Nothobranchius furzeri is an established model species in many fields of research with special emphasis on aging. It is extremely short-lived species that recapitulate standard vertebrate ageing and display spontaneous age-dependent carcinogenesis, an exceptional feature among vertebrates. In pilot experiment with highly inbred and extremely short-lived strain, we confirmed incidence of liver and kidney neoplasia. Our preliminary data from whole exome sequencing indicate that there is considerable number of mutations in genes related to the processes involved in malignant transformation. The aim of the project is to determine driver mutations in tumor suppressor genes and oncogenes and define their role in kidney and liver carcinogenesis. To detect and characterize driver mutations accompanying malignant transformation whole genome sequencing and bioinformatics approaches will be employed. Selected drivers will be evaluated by in vivo CRISPR/Cas9 mutagenesis and N. furzeri proposed as a model of spontaneous (sporadic) carcinogenesis in biomedical research.