Risk of melanoma may be gauged long before suspicious moles appear – study

The risk for melanoma, a deadly skin cancer, can be estimated long before detection of any suspicious moles, new research has suggested.

Skin damage from the sun builds up over time but is not always obvious to the eye.

However, DNA within skin cells also accumulates damage over years of exposure to the sun’s ultraviolet rays and this damage can be measured, according to a new study.

It turns out that a multitude of individual cells in so-called normal skin are riddled with mutations associated with melanoma, which are a result of sun exposure

The research suggests the genomic methods used to probe skin damage could be developed to estimate baseline melanoma risk for individuals in the general population.

They could also be used to make recommendations about how often someone should be screened for cancer by a dermatologist.

Hunter Shain, assistant professor at the University of California, San Francisco’s department of dermatology, said: “It turns out that a multitude of individual cells in so-called normal skin are riddled with mutations associated with melanoma, which are a result of sun exposure.

“Melanoma is an endpoint most often seen only after decades of mutational damage, but some people are at greater risk than others.

“With the techniques we have developed, those who have the most accumulated mutations can be monitored more closely and can choose to better protect themselves from sun exposure.”

Melanoma arises in a type of skin cell called a melanocyte.

These cells make the pigment melanin, which helps protect skin cells, including the much more abundant keratinocytes, from sun damage.

But melanocytes pose the greatest risk when DNA damage causes them to grow out of control.

In the study published in Nature, researchers sequenced melanocyte DNA in skin samples, one cell at a time, to tally mutations, with an emphasis on a handful of mutations that are the main drivers of the emergence and growth of melanoma.

The samples came from six individuals, two melanoma survivors and four cadavers of persons who never had melanoma. All of the people were white.

The researchers analysed DNA from a total of 133 melanocytes from the back, head, legs, shoulder, bottom and feet.

The found that melanocytes from normal skin near the melanoma in the former cancer patients had strikingly more mutations, including melanoma-associated mutations, than skin from the same sites in individuals who never had melanoma.

Prof Shain said people with many moles should still be screened, but only 30% of melanomas arise from pre-existing moles.

He added: “Melanomas really can appear out of nowhere.

“We found out in this work that normal skin contains numerous melanocytes that already exhibit some of the mutations associated with cancer.

“Essentially, we found the precursors to the 70% of melanomas that do not arise from pre-existing moles.”

Prof Shain anticipates that a streamlined, automated version of these methods will one day become widely available to gauge melanoma risk and could serve as the basis for cancer-screening recommendations.