Researchers find gene responsible for rare condition that can lead to melanomas

The genetic cause of a rare condition which causes large moles to grow on the skin and brain before birth and which increases the risk of melanoma, has finally been identified in a study led by the UCL Institute of Child Health (ICH) and Great Ormond Street Hospital (GOSH).

The findings, published in the Journal of Investigative Dermatology, will help clinicians to develop tests for the condition and may help develop treatments for people living with the condition, known as multiple congenital melanocytic naevi or CMN.

CMN can be difficult to live with for children and their families, as the CMN are large dark brown marks on the skin. More seriously, they can also lead to neurological problems such as fits and developmental delay, and to malignant melanoma (skin cancer) which is usually fatal when it occurs.

No treatment is currently available for patients who have many large CMN, but doctors monitor patients carefully for signs of skin cancer, and use MRI to scan the brain for lesions. Small moles can be removed by surgery, but larger areas cannot normally be removed this way. Laser treatment is not a treatment option, as the CMN are too deep to be removed completely.

The breakthrough is the discovery that this condition is caused by a mutation in a gene called NRAS, which occurs while the baby is growing in the womb. The mutation is concentrated in specific parts of the body – it has so far been found in the skin and brain, but not in the blood. This gene mutation was found in 80 per cent of the patients who took part in the study. The other 20 per cent are still being investigated to determine the cause of the condition in their cases.

The gene pinpointed in the ICH-led study is known to be involved in the development of melanomas in the normal population, but has never been found before to occur during the development of a baby. It explains why patients with CMN have an increased risk of melanoma, and the researchers found that the patients need to develop a second mutation to change the moles into cancer.

This is a big breakthrough for people who have CMN. The discovery of the genetic mechanism means we can now develop tests to differentiate between people carrying this gene and those who don’t, and finally we can start to look for new ways to treat this serious condition.

Dr Veronica Kinsler, Paediatric Dermatologist at GOSH and the ICH and lead author of the study