Scientists from the Queensland Institute of Medical Research (QIMR) have found two new genes that together double a person’s risk of developing melanoma.

As part of an international study, a team at QIMR, led by Professors Nick Hayward and Grant Montgomery, studied the genes of almost 6,000 people together with their mole count. Specific changes in two genes were found to make people more susceptible to developing moles. The researchers went on to show, in another 4,000 people, the same two genes increased the risk of developing melanoma - the most deadly form of skin cancer.

“These are the first genes found to increase melanoma risk by influencing the number of moles a person has,” explained Professor Hayward. “This finding improves our understanding of the genetics of melanoma and therefore the molecular pathways that lead to its development.”

“It has long been known that having a large number of moles is the biggest risk factor. Therefore we predicted we would find genes linking moles and melanoma. We now have conclusive genetic evidence that having a large number of moles increases an individual’s risk of developing melanoma.”

The study found that people who carry one of these two gene variants have a 25% increased chance of developing melanoma, while for individuals carrying both variants their risk is doubled.

“In the long term, this research will be useful in developing screening techniques, and will also allow us to identify potential new drug targets and ultimately develop new therapies to treat melanoma,” said Professor Hayward.

Moles are normal but people should seek advice from their doctor if they observe any changes in size, colour or shape. People with lots of moles are at a higher risk of developing melanoma and should therefore take extra care to avoid overexposure to ultraviolet radiation.

Australia has the highest incidence of melanoma in the world with more than 10,000 new cases and 1000 people dying from the disease every year. Queensland has the highest incidence of any state with seven Queenslanders diagnosed with melanoma every day. More than one in 20 Queenslanders is expected to develop melanoma during their lifetime.

The collaborative research involved scientists from the Queensland Institute of Medical Research, King’s College London and The University of Leeds.

The study was funded by the US National Institutes of Health and the Australian National Health and Medical Research Council (NHMRC) and published in Nature Genetics.

Source:
Sarah Tennant

Research Australia

Pinpointing the genes involved in human brain cancer can be like looking for a needle in a haystack, and sometimes the needle you find may not be the right one. By comparing human and canine genomes, researchers at North Carolina State University have discovered that a gene commonly believed to be involved in meningiomas-tumors that affect the meninges, or thin covering, of the human brain and account for one out of four adult brain tumors -may not be as key for tumor formation as previously thought, and they’ve narrowed the search for the real culprit.

Meningiomas are intracranial tumors, meaning that they do not grow within brain tissue itself, but in the space between the brain and the skull. In humans, they are associated with genetic defects of large segments of chromosomes, which makes isolating the specific genes involved extremely difficult. Humans suffering from meningioma frequently lose one copy of almost the entire length of human chromosome 22. This chromosome is made of almost 50 million base pairs of DNA that code for more than 500 genes.

“The dog has been man’s best friend for centuries, and now the genome of the dog could well be man’s next best friend,” says Dr. Matthew Breen, professor of genomics at NC State.

“With so much genetic material to consider, one can see why figuring out which genes play a key role in meningiomas is extremely difficult,” says Breen. “By looking at tumors seen in both humans and dogs we have a simple way to narrow the search: we compare the affected areas of a human chromosome with related areas on dog chromosomes. This works because dogs and humans are genetically similar and both get the same kinds of cancers. While we share much of our genetic material, the DNA of a dog is organized differently to our own and this makes it possible to isolate smaller ’shared’ regions of genetic data rather than looking at an entire chromosome.”

Breen, NC State colleagues Rachael Thomas and veterinary neurologist Natasha Olby, along with researchers from the University of California-Davis and the Wellcome Trust Sanger Institute in Cambridge, UK collaborated on the project, sharing samples of canine meningiomas for research. Their results were published in the Journal of Neurooncology.

Previous researchers had pinpointed a particular tumor-suppressing gene on human chromosome 22, known as NF2, as a possible contributor to meningioma. They believed that the deletion of NF2, with its tumor suppressing abilities, could trigger tumor growth.

In looking at genetic changes across the whole genome, Breen’s team compared human chromosome 22 to its canine counterpart. In dogs, the region shared with 22 is “split up” across three separate dog chromosomes - numbers 10, 26 and 27- with the NF2 gene appearing on dog chromosome 26. The researchers discovered that in dogs with meningioma, chromosome 26, and hence NF2, was rarely affected, casting doubt on this gene as playing a significant role in the disease. Instead, dogs with meningioma frequently showed loss of parts of dog chromosome 27. This led the researchers to focus on the portion of human chromosome 22 that corresponds to canine chromosome 27.

“Now, instead of looking at 50 million base pairs that contain several hundred genes, we can focus on the portion of human chromosome 22 that is evolutionarily conserved with dog chromosome 27,” Breen says. “By looking at dog and human meningiomas together we reduce the amount of searching we need to do 50-fold. It’s the old needle/haystack dilemma, except that using information from dog and human tumors allows us to concentrate our search on the two percent of the haystack that actually contains the needle, and not spend time and resources on the other 98 percent.”

Breen also noticed that the other chromosome involved for canines that suffer from meningioma is dog chromosome 17, which correlates with part of human chromosome 1. Defects of this chromosome are involved in almost 70 percent of human meningioma cases and are associated with a poor patient outcome. He hopes that he can use this correlation to further narrow the search for specific genes involved with the disease.

In addition the team looked also at gliomas, another kind of brain tumor, and have shown common genetic features shared between human and canine tumors that are now under further investigation.

“The data support that dog and human tumors are very similar at the genetic level, so both species will benefit from this research,” Breen says. “It’s proof of the ‘One Medicine’ concept - the idea that human and animal health relies on a common pool of medical and scientific knowledge and is supported by overlapping technologies and discoveries.”

Source:
Tracey Peake

North Carolina State University