Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a disorder that causes the development of benign but often painful tumours in the skin and, in females, in the uterus. Between one in six and one in ten people affected by the disorder will go on to develop an aggressive form of kidney cancer called papillary renal cell cancer. The condition often strikes people in their 20s.
The disorder is caused by mutations, which may be inherited, in a gene responsible for the production of an enzyme known as fumarate hydratase (FH). This leads to an accumulation within cells of fumarate, which promotes the development of cancer cells.
Now, in a study published in the ‘Journal of Pathology’, an international team of scientists led by researchers at the Henry Wellcome Building for Molecular Physiology, University of Oxford, have identified a particular protein modification that is induced by FH deficiency (and hence an over-abundance of fumarate). This alteration is unique to this type of tumour and can hence be used as a biomarker – a biological ‘fingerprint’ to identify tumours caused by this mechanism.
The researchers have developed a test for this protein modification that can be carried out in under two hours and will identify tumours with FH mutations. This approach is much more cost-effective than genetic testing of all possible cases using DNA sequencing. They show that screening cases of papillary renal cell cancer using this new test allows them to identify undiagnosed cases of HLRCC for genetic testing. They believe this test should be applied in all cases of papillary renal cell cancer to identify people with FH mutations, allowing advice to be provided to their families on their own relative risks of developing the disorder and associated kidney cancer.
“Cancer can be caused by many different risk factors, but if we can pinpoint rapidly and accurately the particular type of tumour, we can provide more accurate advice to patients and their families, and perhaps diagnose cases at earlier, more treatable, stages,” explains Dr Patrick Pollard, a Beit Memorial Fellow at the University of Oxford. “For the first time, we are now able to screen for tumours caused by this rare, but often very serious, condition using a test which is simple, cheap and reliable.”
Dr Pollard and colleagues have filed a patent to develop the test, which is currently being marketed by Isis Innovation at the University of Oxford.
Dr Lesley Walker, director of cancer information at Cancer Research UK, said: “We know that diagnosing cancer at an earlier stage offers the best chances of successful treatment. So being able to identify other family members who are at risk so they can be monitored more closely is crucial to improving survival rates from this rare aggressive form of kidney cancer.
“Tests like this can also help us to identify other patients with the same mutation, paving the way for the development of targeted treatments for specific groups of patients. This approach is called stratified medicine and many scientists now believe it could revolutionalise cancer treatment in the future.”
The work was funded by the Wellcome Trust, the Oxford Partnership Comprehensive Biomedical Research Centre, the Department of Health, Cancer Research UK and the National Institutes of Health (USA).
Image: High-magnification micrograph of a clear cell renal cell carcinoma. Credit: Bin Teh, Van Andel Research Institute.
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Notes for editors
Bardella C et al. Aberrant succination of proteins in fumarate hydratase deficient mice and HLRCC patients is a robust biomarker of mutation status. J Pathol 2011 10 May [epub ahead of print].
About the Wellcome Trust
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.
About Cancer Research UK
Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research. The charity’s groundbreaking work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. This work is funded entirely by the public. Cancer Research UK has been at the heart of the progress that has already seen survival rates double in the last forty years. Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses. Together with its partners and supporters, Cancer Research UK’s vision is to beat cancer. For further information about Cancer Research UK’s work or to find out how to support the charity, please call 020 7121 6699 or visit its website.
About Isis Innovation
Isis Innovation is the University of Oxford’s technology transfer company and manages the University’s intellectual property portfolio, working with University researchers on identifying, protecting and marketing technologies through licensing, spin-out company formation and material sales. Isis files on average one new patent application each week, has concluded over 500 technology licensing agreements, and established 70 new spin-out companies from Oxford since 1997. Isis also manages Oxford University Consulting, which arranges consulting services providing clients access to the world-class expertise of the University’s academics to enhance innovative capability. Last year OUC arranged over 150 consulting deals. Isis has a separate business division, Isis Enterprise, offering consulting expertise and advice in technology transfer and open innovation to university, government and industrial clients around the world. Isis was founded in 1987 and is today one of the world’s leading technology transfer and innovation management companies.