Driver mutations in cancer genome of Nothobranchius furzeri: from tumor biology to concept of experimental model of spontaneous carcinogenesis (2019–2021)

Číslo projektu 19-20873S
Období 1. 1. 2019 — 31. 12. 2021

African annual killifish Nothobranchius furzeri is an established model species in many fields of research with special emphasis on aging. It is shortest-lived and rapidly aging species with spontaneous age-dependent carcinogenesis, what makes N. furzeri exceptional among vertebrates. In pilot experiment with highly inbred and extremely short-lived strain we already described incidence of liver and kidney neoplasia. According to our preliminary data from new generation sequencing (exome sequencing), there is considerable number of mutations in genes related to the processes involved in malignant transformation. The aim of present project is to discover driver mutations in tumour suppressor genes and oncogenes and verify their role in kidney and liver tissue carcinogenesis. To detect and characterise key mutations accompanying malignant transformation whole genome sequencing (WGS) will be used. Finally, we will assess the role of selected candidate oncogenes and tumour suppressor genes in vivo by CRIPR/Cas9 mutagenesis of N. furzeri.