Genetic changes linked to adult kidney cancer can occur in childhood

Researchers at the Wellcome Sanger Institute have discovered that key genetic changes which may lead to kidney cancer can occur as early as childhood or adolescence. This can be up to 50 years before the disease is diagnosed.

Coloured model of human kidney.
Researchers used sequencing techniques to analyse the genomes of 95 tumours from 33 patients.
Credit: Phospho Biomedical Animation

Kidney cancer is the 7th most common cancer in the UK and its incidence has more than doubled in the past decade. 

The researchers hope these new findings will help to identify opportunities for earlier monitoring and intervention in the treatment of kidney cancer. 

Distinctive genetic damage

Many patients with kidney cancer show distinctive genetic damage in their cells. The researchers used sequencing techniques to analyse the genomes of 95 tumours from 33 patients to identify when these major genetic faults occurred.

The genetic changes occur at the chromosomal level with just a single genetic event causing the loss of hundreds of genes in childhood or adolescence. 

The researchers found that only a few hundred cells carry these genetic changes and the cells are likely to be common to most of the population. 

The cells remain dormant unless further genetic mutations cause them to trigger the disease – only 1-2% of people develop kidney cancer. Further mutations can be caused by smoking, obesity or an inherited risk of kidney cancer. 

The new findings, published today in Cell, are part of a trio of papers produced by the TRACERx Renal consortium. It aims to better identify the drivers and differences between kidney cancers to help improve treatment options. TRACERx is made up of researchers and clinicians from the Francis Crick Institute, UCL, Royal Marsden NHS Foundation Trust, and Guy’s and St Thomas’ NHS Foundation Trust.  

Three evolutionary paths for tumours

The two other studies identified three distinct evolutionary paths for kidney cancer. Each type is characterised by the order in which they acquire distinct genetic changes.

  • Type 1 tumours show little genetic damage and never acquire the ability to become aggressive, invasive tumours.
  • Type 2 tumours experience rapid bursts of chromosomal changes. They grow rapidly and often spread to multiple other organs. 
  • Type 3 tumours gradually accumulate these genetic changes and typically spread to only one other place in the body. 

These new findings help researchers to understand why patients with similar diagnoses show variations in their prognosis and response to treatments. 

The researchers hope their work will lead to better informed treatment plans and more personalised interventions.  

More information

  • Read the research papers published in Cell:

Timing the landmark events in the evolution of clear cell renal cell cancer: TRACERx Renal

Deterministic evolutionary trajectories influence primary tumour growth: the TRACERx Renal study

Tracking renal cancer evolution reveals constrained routes to metastases, results from the TRACERx Renal study

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