Kidney cancer linked to gene mutation

Scientists have discovered a mutated gene in one in three people with the most common form of kidney cancer.

The mutation, carried in a gene called PBRM1, was found in 88 of 257 cases of clear cell carcinomas, making it the most common mutation to be identified in kidney cancer for 20 years.

The scientists suspect the mutated BPRM1 gene may act in combination with another to drive the disease.

"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,” said Dr Andy Futreal, Head of Cancer Genetics and Genomics at the Wellcome Trust Sanger Institute, one of the teams involved in the study.

“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.”

The PBRM1 gene is found on chromosome 3, in the same region as two other known kidney cancer genes, including VHL. The fact that the genes are linked in their location may allow the cancer to exploit our biology, say the researchers, by reducing the number of genetic events needed to hit and inactivate all three genes.

Many kidney cancer patients carry mutations in two, if not all three of the genes in this region.

All three genes also have similar functions; they help hold the DNA in cells together and are also involved in cell division and repair which is why faults in the genes could lead to cancerous cells developing.

“Over the last year, our understanding of how kidney cancer develops had already markedly improved through identification of three new mutated cancer genes, each of which makes a small contribution to the disease,” said Professor Mike Stratton, Director of the Sanger Institute.

“Now, our discovery of PBRM1 mutations in one in three kidney cancers is a major advance. 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.”

The research was carried out at the Wellcome Trust Sanger Institute, UK; the Van Andel Research Institute of Grand Rapids, Michigan, and the National Cancer Centre of Singapore.

The findings are published in the journal Nature.

This article was published on Thu 20 January 2011