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Work from the Ratcliffe research group demonstrates the early events defining the cell-type specificity of oncogenesis, providing a focus for mechanistic understanding and therapeutic targeting.

Research from the Ratcliffe research team, led jointly by Samvid Kurlekar and Joanna Lima has suggested that early events, even in advance of morphological abnormality, shape the cell-type specificity of oncogenesis. The team have studied the changes induced by loss of the tumour suppressor gene von Hippel Lindau (VHL), which ultimately drives clear cell renal cell carcinoma. By employing single-cell analyses of heterogenous and dynamic responses to VHL inactivation in the kidney, the Ratcliffe group have defined a proximal tubular cell class with oncogenic potential, and revealed longer term adaptive changes in areas of the renal cell layers.

By creating a new oncogenic cell tagging model of Vhl loss, and combining it with existing wild-type or defective VHL alleles, the researchers developed a comparative against which the evolution of changes following biallelic VHL inactivation can be assessed. From this comparison, they describe for the first time the effects of VHL inactivation at cellular resolution in the native kidney context, adding to the understanding of VHL-associated tumour suppressor functions in several different ways.

To find out more, see the full paper in Cancer Research