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A study from the Ratcliffe research group of NDM’s Ludwig Institute for Cancer Research has demonstrated the early events defining the cell-type specificity of the development of a tumour, providing a focus for mechanistic understanding and therapeutic targeting.

The research was led jointly by Samvid Kurlekar and Joanna Lima from the research group of Professor Sir Peter Ratcliffe, Professor of Clinical Medicine at the Ludwig Institute for Cancer Research. The study 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 the 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. The study was published in Cancer Research.

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.

Read the full paper here: