Mutation Burden in Normal Skin as a Predictor of Melanoma Risk
Abstract
Melanoma is the deadliest form of skin cancer, accounting for an estimated 55,000 deaths worldwide per year. Skin screening can identify melanocytic neoplasms in their early stages of progression, before they become lethal; however, it is not feasible to conduct skin screens over the entire population on a regular basis. As it stands, many people with little risk of melanoma are being screened too often, placing an undue burden on our medical system, while many other people at high risk of melanoma are not being screened at all. Establishing biomarkers that could quantify melanoma risk on an individual basis would allow for personalized screening and prevention measures. Towards this goal, we hypothesize that the mutation burden of normal skin cells directly correlates with the risk of developing melanoma. Known risk factors for melanoma include light skin tone and high levels of sun exposure. Melanomas on the sun-exposed skin are riddled with mutations from sunlight. Collectively, these observations imply that the risk of melanoma increases as skin cells accumulate more and more mutations from sun exposure. Directly measuring the average number of mutations in each normal skin cell would reveal the cumulative level of DNA damage in an individual’s skin. This information could then be harnessed to provide personalized guidance on how to prevent skin cancer moving forward. Testing this hypothesis is complicated by the fact that it is difficult to measure mutations in individual cells. We have recently overcome this hurdle and developed solutions to produce reliable mutation estimates in individual cells of normal human skin. We will further develop these strategies into a prototype clinical assay, and then we will measure the mutation burdens of skin samples both from people with melanoma and without melanoma, matched for age and body site. Completion of these studies will determine whether the number of acquired mutations in skin cells can help predict the risk of an individual to develop a melanoma in the future. Overall, these studies open a promising new avenue of research for the cancer prevention community, in-line with the goals of the Melanoma Research Program. Fiscal Year 2021 Melanoma Research Program Focus Areas addressed: Our proposal addresses four Focus Areas, rank ordered below by their relevance to our proposal. * Identify and understand risk factor determinants for melanoma, including variants (e.g., uveal, acral, mucosal melanoma). * Understand how precursor lesions and endogenous host factors may lead to melanomagenesis. * Develop prediction and surveillance tools for distinguishing patient at risk for recurrence and/or metastasis. Identify biological determinants to differentiate patient populations. * Identify methods to decrease risk of melanoma development beyond sunscreen and protective clothing.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210525
Entities
People
- Boris Bastian
Organizations
- United States Army
- University of California, San Francisco