A rare genetic change could help scientists determine which genes are involved in how people develop certain cancers, but it may also lead to a new way to treat the condition.
A new study in the journal Nature Medicine describes the findings of two British researchers who discovered a genetic mutation in mice that leads to a rare form of human cancers called myeloma, the most common type of blood cancer in the world.
In mice, myelomas have no immune system to attack, but a mutated gene is the only thing that makes them more susceptible to infection by the immune system.
“The mutations cause a very rare type known as a non-small cell lung cancer,” said Dr. Mark Hulme, a member of the Oxford Medical Sciences team.
The researchers discovered the mutation in two mice that had been genetically altered in the laboratory.
In this case, the mutation was in the gene for a protein called c-Myc, which regulates the activity of a protein in the immune cells of a cell called the phagocytic cell.
“In this way, the non-mammalian cell in which it is found, called the cytotoxic T lymphocytes, becomes a target for the tumour,” Hulmes said.
In the new study, Hulkes’ team also found that a genetic alteration in mice causes a rare mutation in the C-Myg gene, which is one of the proteins that helps the immune response to fight against foreign invaders.
“We found that this gene is involved in two very different cancers, the first of which is a rare type called the non human large cell lymphoma, or NLCL,” he said.
“When we altered the mice’s environment, we found that they developed lung cancer more rapidly, and that these cancers were more lethal to mice that were raised in the presence of this mutation.”
The scientists also found the mutation to be passed down from parent to offspring.
“Our study shows that our findings may provide the first direct evidence that an unusual gene mutation can be responsible for a rare genetic disease,” said Hulms co-author and researcher Dr. Michael Mather.
Mather is the chief scientific officer at British pharmaceutical company Roche, which has been researching the molecular mechanisms of human disease for the past 30 years.
“There are a lot of different mechanisms that can be involved,” he explained.
“For example, it’s possible that one mutation could predispose to certain cancers by preventing the production of certain genes that are necessary for the development of those cancers.”
Other mechanisms could involve the formation of new proteins that cause the same effect.
We think it’s a combination of all of these different possibilities.
“Mather said the study was a “huge step forward” in understanding how the human genome functions.”
This is the first time that we have been able to isolate the CMT gene from the mouse genome and then show that this particular mutation affects the normal functioning of the C MT gene in a very particular way,” he added.
In addition to Hulles research, Mather and his colleagues published a study in Nature earlier this year showing that the same mutation could lead to rare cancers in the lungs of people with a rare skin condition called polycystic ovarian syndrome.”
It’s a very exciting discovery,” said Mather, who also works at Roche.”
Now we can see what happens when this mutation is switched on in different mice, so we can start to understand exactly what it is that is going on.
“We hope that this will help to develop better therapies for rare genetic diseases.”
In this study, researchers found that the mutation leads to tumors in mice with polycytic ovarian syndrome that can grow much larger than normal, and cause death in up to 80 per cent of patients.
This new research suggests the discovery of a rare gene mutation that may be able to help treat a rare disease may have potential applications in the clinic, Hulets co-authors said.
They hope that the discovery could also lead scientists to develop new medicines that target the genes involved in cancer development.
“At the moment, it is very difficult to find these rare mutations in human genomes, because the gene sequences are very small, so they are difficult to sequence and look at,” Huless said.
“With our work, we have discovered a way of making it possible to sequence the human genomes.”