Comprehensive genomic analysis of tumour and host interactions in the genesis of kidney cancer

Renal cell cancer (RCC) is the 7th commonest cancer and the most lethal urological malignancy with 50% of patients dying from their disease.

Small renal masses (SRMs; <4cm) represent a stage of RCC where progression and prognosis varies. Some SRMs never need intervention but current standard of care is surgical resection with significant risks. There is an urgent unmet clinical need to identify, at the point of diagnosis, which are likely to progress, and which are unlikely to cause future harm and avoid over-treatment.

This project will use novel DNA and RNA ‘molecular archaeology’ techniques (that look at current genomic evidence to understand past key genomic events that led to cancer) to time when these events occurred (n=240 patients) in RCCs.

By mapping molecular archaeology with tumour growth rates from 3D CT images we will identify whether the timing of genomic events can assess progression once an RCC is detected. We will also determine whether the downstream effects of key genomic events (using RNAseq and TCRseq) correlate with progression and the timing of the earliest progression defining changes.

The project will use paired blood, multi-region sampled RCCs and normal kidney, and serial CT scans from two complementary translational research trials at the UK’s highest volume RCC centres in a new collaboration. This will enable development of a multiparametric test to allow clinicians to tailor treatment according to how we think their tumour will progress and, if detectable in blood, addresses the urgent need to develop an RCC screening test.