Sunday 17 March 2013
Scientists have identified a brand new genetic mechanism that raises the risk of cancer via a domino effect on DNA – with one gene fault triggering a second, cancer-causing mutation.
A team at The Institute of Cancer Research, London, found some cancer patients inherit a weak point in their DNA that appears to leave one of their chromosomes vulnerable to snapping and becoming mutated.
Researchers hailed the finding - published in Nature Genetics today (Sunday) - as a “very important discovery” that opens up new avenues for cancer treatment and prevention.
Their study sheds new light on the causes of a blood cancer called multiple myeloma – which affects around 4,700 patients in the UK each year - and could have implications for other types of cancer too.
It is the first time scientists have found evidence that inheritance of a gene fault can increase the risk of suffering a specific chromosomal mutation – in this case one that can drive development of cancer.
The study was funded by a number of organisations, including Myeloma UK, Leukaemia & Lymphoma Research, Cancer Research UK and via the NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research.
It assessed the DNA of 1,655 patients with myeloma and compared them with people in the general population, in order to explore whether they had inherited genetic faults that had increased their risk of developing the disease.
Researchers found that inheritance of a specific DNA change termed CCND1 G870A was associated with an 80% increase in the risk of developing a sub-type of myeloma affecting about a fifth of patients.
This sub-type is known to be triggered by a specific chromosomal translocation – a type of DNA breakage and rearrangement - designated by the code t(11;14). The translocation forms a mutant piece of DNA that drives cancer by activating several genes.
Study author Professor Richard Houlston, Professor of Molecular and Population Genetics at the Institute of Cancer Research, said: “We’ve uncovered a new way in which genetics can raise the risk of developing cancer, in which ne gene fault appears to trigger another – in a domino-like effect.
“It’s the first time anyone has identified a specific gene fault that raises the risk of developing a second specific type of DNA damage. Not only is the discovery valuable for our understanding of multiple myeloma, but it also demonstrates the value of studying specific genetic sub-types of cancer, rather than grouping them all together as one disease.”
Co-author Professor Gareth Morgan, Head of Molecular Haematology at The Institute of Cancer Research and Head of the Myeloma Unit at The Royal Marsden, said: ‘This is a very important discovery, which opens out our understanding of cancer genetics and gives us new avenues for treatment and prevention.
“Now that we have found a genetic risk factor for a particular sub-type of multiple myeloma, I’m hopeful we can design more targeted treatments for the people who develop it. In cancer research we tend to group different sub-types together, but this research proves we need to move away from this approach and investigate sub-types at a molecular level.”
Eric Low, Chief Executive at Myeloma UK, said: “We are very pleased that Myeloma UK funded research at the ICR has resulted in another important discovery. These findings have opened up new directions for research that will help understand how myeloma develops and help identify new targets for treatment. In the future, it may be possible to identify those people most at risk of developing myeloma. Myeloma UK is already funding a follow-up project at the ICR to take these important discoveries to the next stage.”
Professor Chris Bunce, Research Director at Leukaemia & Lymphoma Research, said: “Myeloma is a devastating blood cancer, which as well as almost always being fatal, causes debilitating and painful bone damage. By establishing exactly how inherited genetic factors cause myeloma in many cases, this breakthrough research could lead to the development of individualised treatment for a significant group of patients.”
The study was conducted in conjunction with a group of scientists at the University of Heidelberg in Germany and is the largest study of its kind investigating inherited predisposition to multiple myeloma.
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Notes to editors
* Multiple myeloma is the third most common type of blood cancer, with around 4,700 new cases and around 2,600 deaths each year in the UK. It is a cancer of blood cells that tend to localise to the bone marrow.
About The Institute of Cancer Research
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 www.icr.ac.uk
About The Royal Marsden
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.
For more information, visit www.royalmarsden.nhs.uk or contact Naomi Owen on 0207 808 2107 or [email protected]