Searching for the Cause

Categories: CMN Research
Mark Beckwith, Veronica Kinsler, Megan Stewart, Valérie Morgan.

At the American Society of Human Genetics Annual Meeting. L-R: Mark Beckwith, Executive Director of Nevus Outreach, Dr. Veronica Kinsler, Megan Stewart, a young woman with a large CMN, and Valérie Morgan, mother of a child with CMN and a supporter of Nevus Outreach.

On Friday, November 9, 2012, noted nevus scientist Veronica Kinsler of Great Ormond Street Hospital in London presented an important discovery at the Annual Meeting of the American Society for Human Genetics in San Francisco. This discovery may speed up the ongoing search for ways to help people affected by congenital melanocytic nevi and neurocutaneous melanocytosis.

Dr. Kinsler and others have been on the trail of what causes congenital melanocytic nevi (CMN), thanks in part to the support of Nevus Outreach in the United States, and Caring Matters Now in the United Kingdom, support which would not be possible without the dedication of the families of people affected by this rare disease. 

At the American Society of Human Genetics 2012 Annual Meeting, Dr. Kinsler had been invited to present her findings which focus on the idea that a congenital melanocytic nevus might be the result of a genetic mutation that takes place at some point after conception (called a “somatic mutation”), and therefore is not a genetic failing passed from a parent to a child, which would be present at conception. She confirmed that in 80% of the patients in the study, her team found the same mutation, and proposed that the remaining 20% will be the result of a different (somatic) mutation event (which would also take place after conception), which she and her team may be equipped to discover. 

The mutated gene present in 80% of the patients is called NRAS, which has been on the short list of suspects for a number of years. 

Technique Had to Catch Up

“We looked at NRAS nearly three years ago, but because we didn’t have conclusive results, we shelved it for a couple of years.” It was through the team’s relatively recent ability to amplify the mutation in the laboratory setting that Kinsler discovered NRAS was worth a second look. “Sure enough, we found mutations coming out of the woodwork,” she explained. 

What Does This Mean for the Future? 

Melanoma is one of the two main causes of nevus-related death for people who have CMN. It is good news that NRAS is already a relatively well-known gene in the world of melanoma, and there are already a number of therapies that have been developed to treat this aggressive cancer. 

Veronica Kinsler at the Great Ormond Street Hospital for Children.

Veronica Kinsler at the Great Ormond Street Hospital for Children.

Dr. Kinsler’s team in the UK has begun the process of methodically testing known NRAS drugs now that they have a target to aim for. “Steering patients toward the right drugs could be very helpful,” Dr. Kinsler reported, with cautious optimism. The process of taking potential cures from the bench to the bedside takes a lot of time and a lot of effort. She explains, “When we have figured out which drugs may work, we will propose clinical drug trials, which will involve people with nevi from all around the world.” 

She described how, once a genetic marker is discovered, drugs could target the specific mutation, which could reduce side effects to cells that don’t have the mutation, resulting in a therapy that is both effective and has minimal side-effects. 

After her presentation, she thanked the Wellcome Trust and the English patient association Caring Matters Now for their ongoing support of this research. She closed with an acknowledgment of the contributions of Rudolf Happle, who was one of the speakers at the Nevus Outreach-sponsored 2011 International Expert Meeting in Tübingen, Germany. “Dr. Happle hypothesized in 1997 that CMN would turn out to be a somatic event. It turned out he was exactly right.”

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