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Scientists Identify Gene Fault With A Domino Effect On Cancer Risk

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 , 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 – 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 , Leukaemia & Lymphoma Research, Cancer Research UK and via the NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust.

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 one 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.

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.


Source: The Institute of Cancer Research