Study identifies common gene fault in kidney cancer

In collaboration with Adfero

A new study, part-funded by Cancer Research UK, has identified a gene that is faulty in one-third of patients with the most common form of kidney cancer - clear cell renal cell carcinoma (ccRCC).

Results published in the journal Nature describe how scientists found that a gene called PBRM1 was altered, or 'mutated', in 88 of the 257 ccRCC cases they analysed.

The faulty version of the gene is the most prevalent to be identified in kidney cancer for 20 years and its discovery could provide new clues to treating the disease.

Dr Andy Futreal, head of cancer genetics and genomics and co-head of the Cancer Genome Project at the Wellcome Trust Sanger Institute, revealed: "Until recently, when we talked about the genetics of renal carcinoma we would inevitably be talking about VHL - a gene mutated in eight out of ten patients.

"But we knew this was likely not to be the full story - so the question we have sought to answer is which genes are conspiring with VHL to cause the disease we see in patients? Over the last year or so, we have started to assemble that puzzle - this research provides a new and critical piece."

According to the research team, which also included scientists at the Van Andel Research Institute in the US and the National Cancer Centre of Singapore, faults in the PBRM1 gene appear to inactivate a protein that is required for the repair of damaged DNA, the control of cell growth, and to turn other genes on and off.

The gene is located on a region of chromosome 3 that also contains the well-established VHL kidney cancer gene and the recently identified gene SETD2.

Many of the patients involved in the study were found to have faults in two, if not all three, of these genes.

Professor Mike Stratton, director of the Sanger Institute and co-head of the Cancer Genome Project, revealed that our understanding of kidney cancer has improved "markedly" over the last year, thanks to the identification of three new mutated cancer genes.

"Now, our discovery of PBRM1 mutations in one in three kidney cancers is a major advance," he said.

"We think we may have an almost complete understanding of the set of abnormal genes that drive this cancer and our understanding of the disease has been transformed by the realisation that most of these genes are involved in providing the structure that encases DNA in the cell and that regulates its function. This insight will provide us with many new therapeutic directions for this cancer."

Dr Julie Sharp, senior science information manager at Cancer Research UK, said: "This research gives us a better overall picture of the key gene faults that drive kidney cancer, providing vital clues that will help scientists and doctors to design new ways to tackle this disease in the future."


  • Varela, I. et al (2011). Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma Nature DOI: 10.1038/nature09639