Public Release: 

Major study links gene to drug resistance in testicular cancer

Institute of Cancer Research

A major research study has uncovered several new genetic mutations that could drive testicular cancer - and also identified a gene which may contribute to tumours becoming resistant to current treatments.

The study is the first to use state-of-the-art sequencing technology to explore in detail testicular germ cell tumours - which make up the vast majority of testicular cancers and are the most common cancers in young men.

It was led by scientists at The Institute of Cancer Research, London, and funded by the Movember Foundation.

The researchers, whose study was published in Nature Communications today (Thursday), used a genetic technique called whole-exome sequencing to examine tumour samples from 42 patients with testicular cancer treated at the Royal Marsden NHS Foundation Trust.

They uncovered a number of new chromosome duplications and other abnormalities that could contribute to the development of this cancer, as well as confirming a previous association with the gene KIT.

Their study also found defective copies of a DNA repair gene called XRCC2 in a patient who had become resistant to platinum-based chemotherapy. They were able to verify the link between XRCC2 and platinum resistance by sequencing an additional sample from another platinum-resistant tumour.

Although generally testicular cancer responds well to treatment, resistance to platinum-based chemotherapy is associated with a poor long-term survival rate. The research provides a clue to why around 3 per cent of patients develop resistance to platinum chemotherapy, as well as new insights into testicular germ cell tumours generally.

Dr Clare Turnbull, Team Leader in Predisposition and Translational Genetics at The Institute of Cancer Research, London, and Honorary Consultant in Clinical Genetics at The Royal Marsden NHS Foundation Trust, said:

"Our study is the largest comprehensive sequencing study of testicular tumours published to date, describing their mutational profile in greater detail than has been possible using previous technologies. We have identified new potential driver mutations for this type of cancer, and provided new evidence of a link between mutations in the gene XRCC2 and platinum treatment-resistant tumours.

"We now need additional studies with a larger number of patients, focusing in particular on platinum-resistant tumours, to help our discoveries lead to new options for those unlucky men whose cancer progresses in spite of the best available treatments."

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

"This study has used the latest DNA sequencing technologies to provide a window into the development of testicular cancer, and reveals some potentially important clues as to how the disease could be treated more effectively.

"Survival rates for testicular cancer are generally very good, but a subset of men don't respond to standard platinum chemotherapy, and the new research has identified a possible genetic cause for that drug resistance. Knowing which are the key genes driving a cancer's development or helping it dodge the effects of chemotherapy is crucial to help us use existing drugs more effectively and to design the next generation of drugs for personalized medicine."

Paul Villanti, Executive Director of Programs, Movember Foundation, said:

"As a strategic funder of over 580 men's health programs around the world, we recognise the significance of this development and are proud to have been able to provide funding. Understanding the risk factors for developing a testicular cancer and also what is different in the tumours of men who don't respond to chemotherapy is a critical piece of the puzzle and moves us one step closer to the Movember Foundation's goal of having an everlasting impact on the face of men's health.

Dr Turnbull and her colleagues should be incredibly proud of the progress they are making and, while there is still a great deal of work to be done, they're making the Movember community confident in the knowledge that funds they've raised are genuinely and positively impacting the lives of men."

###

Notes to editors

For more information contact Claire Hastings, Media Officer at ICR, on 020 7153 5380 / chastings@icr.ac.uk. For enquiries out of hours, please call 07595963613.

The Institute of Cancer Research, London, is one of the world's most influential cancer research institutes.

Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients' lives. Through its unique partnership with The Royal Marsden NHS Foundation Trust and 'bench-to-bedside' approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four cancer centres globally.

The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it leads the world at isolating cancer-related genes and discovering new targeted drugs for personalised cancer treatment.

As a college of the University of London, the ICR provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.

The ICR's mission is to make the discoveries that defeat cancer. For more information visit http://www.icr.ac.uk

About the Movember Foundation

The Movember Foundation is a global men's health charity which raises vital funds and awareness for the often ignored issues of men's health, specifically prostate cancer, testicular cancer and men's mental health. It is responsible for the sprouting of millions of moustaches around the world in November when men become walking talking billboards for men's health. Mo Bros start the month clean-shaven, and then grow and groom their moustache all month long.

Funds are directed to men's health programmes which are shaped by Movember's vision to have an everlasting impact on the face of men's health.

Programme areas focus on awareness and education, living with and beyond cancer, staying mentally healthy and research. Programmes are delivered by the Movember Foundation and its men's health partners in each country. Further information about how Movember's funds are invested can be found at Movember.com

The Movember journey began in 2003 with a few mates in a pub in Melbourne, Australia. The goal was simple - to create a campaign promoting the growth of the moustache among like-minded people and have fun along the way. It is about real men growing real moustaches, talking about real issues to help to change the face of men's health.

Movember now spans the globe across 21 countries. Since inception, a global army of 5 million Mo Bros and Mo Sistas have grown, or supported the growth of a moustache. To date almost £400 million has been raised globally and over 800 men's health projects are being funded.

For more information on Movember visit http://www.movember.com

Further enquiries on Movember contact: Paul Mitcheson on 07944 792300 - mitch@movember.com

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.