Scientists have identified a brand new genetic mechanism that raises the risk of myeloma 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 myeloma 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 - as a “very important discovery” that opens up new avenues for cancer treatment and prevention.
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, Myeloma UK and via the NIHR Biological Research Centre at The Royal Marsden Hospital NHS 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 hopefully 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.”
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.