Accumulated genetic damage could predict melanoma risk
Risk of future melanoma can be estimated by evaluating accumulated sun damage-induced mutations in non-lesional skin, researchers report online in Nature (Oct. 7, 2020).
In a press release from the University of California San Francisco (UCSF), the authors of the paper say that the genomic methods they used to probe skin damage in their study could be developed to be used to estimate baseline melanoma risk for individuals in the general population. Based on those estimates, recommendations could be made about how often an individual should be screened for cancer by a dermatologist.
“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,” said senior author A. Hunter Shain, PhD, in the release. “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.”
Dr. Shain is a member of the UCSF Helen Diller Family Comprehensive Cancer Center, and an assistant professor in UCSF’s Department of Dermatology.
In their study, Dr. Shain and his colleagues sequenced the DNA of melanocytes in skin samples taken from two melanoma survivors, and four cadavers of individuals who had never had melanoma. The investigators analyzed DNA from a total of 133 melanocytes taken from the back, head, legs, shoulder, buttocks and feet, tallying mutations. Their main focus was on mutations known to be the main drivers of the emergence and growth of melanoma.
They 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.
While emphasizing that people with many moles should still be screened for skin cancers, Dr. Shain noted that just 30% of melanomas arise from pre-existing moles.
“Melanomas really can appear out of nowhere,” he said. “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 per cent of melanomas that do not arise from pre-existing moles.”
Dr. Shain noted that there are many factors that contribute to melanoma risk in a complex way. Some are environmental, such as childhood sunburns or adult occupational exposure, and others are genetic such as skin tone or inherent DNA-repair capacity, he said. Because of this complexity, measuring mutations may be a good way to look at the net effect of all the variables.
Consistent with the known pattern of melanoma occurring more often on intermittently sun-exposed areas of the skin compared to chronically exposed areas, the research team found more mutations in melanocytes from the back and limbs than in skin from the head and neck.