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Scientists discover intriguing new gene link to breast and ovarian cancer


Sunday 16 December 2012


A team of researchers led from The Institute of Cancer Research, London, have found that mutations in a gene called PPM1D are linked to an increased risk of breast and ovarian cancer – through what may be a new mechanism of cancer development.

Women with PPM1D mutations have a 20 per cent chance of developing breast or ovarian cancer – double the breast cancer risk and over 10 times the ovarian cancer risk of women in the general population.

The discovery could have implications for genetic testing and targeted prevention in particular for ovarian cancer, which is often diagnosed at an advanced stage.

And intriguingly, PPM1D seems to be working in a completely different way to other genes known to increase the risk of breast and ovarian cancer, such as BRCA1 and BRCA2.

We have two copies of every gene. In most cancer-causing genes a mutation in one copy is inherited and present in every cell, with the second copy mutated in the tumour itself.

However, in this case the team found PPM1D mutations were not inherited and rather than being present in every cell, were only found in blood cells.

Even more surprisingly, there were no PPM1D mutations in the cancer cells or in the normal breast or ovarian cells.

The mutations make PPM1D overactive, which in turn reduces the action of a gene called TP53, which is the most frequently mutated gene in cancer cells.

This important discovery is published in the journal Nature this week, and may signify a new cancer-causing mechanism.

Study leader Professor Nazneen Rahman, head of genetics at The Institute of Cancer Research (ICR) and head of the cancer genetics clinical unit at The Royal Marsden NHS Foundation Trust, said: “This is one of our most interesting and exciting discoveries. At every stage the results were different from the accepted theories. We don’t yet know exactly how PPM1D mutations are linked to breast and ovarian cancer, but this finding is stimulating radical new thoughts about the way genes and cancer can be related.

“The results could also be useful in the clinic, particularly for ovarian cancer which is often diagnosed at an advanced stage. If a woman knew she carried a PPM1D mutation and had a one in five chance of developing ovarian cancer, she might consider keyhole surgery to remove her ovaries after completing her family.”

Revolutionary new sequencing technologies that allow much deeper analysis of genes were crucial to the discovery. The PPM1D mutations were only present in some cells – a so-called mosaic pattern, which is difficult to detect with older sequencing methods. It is very possible that similar mosaic mutations in other genes, and in patients with other types of cancer, will emerge as many groups are now doing deep sequencing research.

The team analysed 507 genes involved in DNA repair in 1,150 women with breast or ovarian cancer, identifying PPM1D gene mutations in five women. They then sequenced the PPM1D gene in 7,781 women with breast or ovarian cancer and 5,861 people from the general population. There were 25 faults in the PPM1D gene in women with cancer and only one in the general population, a highly statistically significant difference.

Professor Alan Ashworth, chief executive of The Institute of Cancer Research and one of the study researchers, said: “This discovery really does turn conventional wisdom about the way genetic mutations can lead to cancer on its head. As we unravel this puzzle, we are likely to gain valuable insights about how cancer develops, and new tools for assessing people’s risk of the disease and targeting preventive treatment.”

The study was funded by the ICR, the Wellcome Trust, Cancer Research UK and Breakthrough Breast Cancer.

Dr Michael Dunn, Head of Molecular and Physiological Sciences at the Wellcome Trust said: “This study is a fantastic example of the power of next generation sequencing to discover new cancer predisposing genes, offering opportunities for better diagnosis. The discovery also opens up a very exciting new avenue of research in the study of cancer development."




Media contact: ICR PR Manager Tatjana Trposka on 020 7153 5312 or 07780689891(out of hours).


Notes to editors

Breast cancer is the most common cancer in the UK with almost 50,000 new cases diagnosed each year. Ovarian cancer is the fifth most common cancer in women – almost 7,000 cases are diagnosed annually in the UK.

Last year a team at The Institute of Cancer Research led by Professor Rahman showed that mutations in two genes called RAD51D and RAD51C increase the risk of ovarian cancer. Their previous work has also led to the discovery of four breast cancer genes, ATM, CHEK2, BRIP1 and PALB2.


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 Hospital 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


The Royal Marsden opened its doors in 1851 as the world’s first hospital dedicated to cancer diagnosis, treatment, research and education.

Today, together with its academic partner, The Institute of Cancer Research (ICR), it is the largest and most comprehensive cancer centre in Europe treating over 44,000 patients every year.  It is a centre of excellence with an international reputation for groundbreaking research and pioneering the very latest in cancer treatments and technologies. The Royal Marsden also provides community services in the London boroughs of Sutton and Merton and in June 2010, along with the ICR, the Trust launched a new academic partnership with Mount Vernon Cancer Centre in Middlesex.

Since 2004, the hospital’s charity, The Royal Marsden Cancer Charity, has helped raise over £50 million to build theatres, diagnostic centres, and drug development units. Prince William became President of The Royal Marsden in 2007, following a long royal connection with the hospital.

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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.

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