BRAF mutations in cutaneous melanoma are independently associated with age, anatomic site of the primary tumor, and the degree of solar elastosis at the primary tumor site
Open accessAbstract
Summary: Oncogenic BRAF mutations are more frequent in cutaneous melanoma occurring at sites with little or moderate sun‐induced damage than at sites with severe cumulative solar ultraviolet (UV) damage. We studied cutaneous melanomas from geographic regions with different levels of ambient UV radiation to delineate the relative effects of cumulative UV damage, age, and anatomic site on the frequency of BRAF mutations. We show that BRAF ‐mutated melanomas occur in a younger age group on skin without marked solar elastosis and less frequently affect the head and neck area, compared to melanomas without BRAF mutations. The findings indicate that BRAF ‐mutated melanomas arise early in life at low cumulative UV doses, whereas melanomas without BRAF mutations require accumulation of high UV doses over time. The effect of anatomic site on the mutation spectrum further suggests regional differences among cutaneous melanocytes.
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The activating Braf V600E mutation, which is common in melanoma, is typical of an oxidative stress-induced mutation.
“The activating Braf V600E mutation, which is common in melanoma, is typical of an oxidative stress-induced mutation [ 18 , 19 ].”
From Differential Induction of Reactive Oxygen Species and Expression of Antioxidant Enzymes in Human Melanocytes Correlate with Melanin Content: Implications on the Response to Solar UV and Melanoma Susceptibility (2022) · cites this paper as [19]
The Introduction (page unavailable) describes activating BRAF mutations as common in cutaneous melanoma, and the Results report BRAF mutations in 50.5% and 39.2% of the two cohorts. But the paper does not identify V600E as a typical oxidative stress-induced mutation; its Abstract instead associates BRAF-mutant melanomas with low cumulative UV damage. Searches for “oxidative stress-induced mutation” and “V600E mutation oxidative stress” found no support for that mechanism. (LLM, conf=0.87)
Experimental — accuracy not yet measuredBRAF and NRAS mutations are not UV-signature mutations but are more common in sun-exposed skin.
“While these mutations are not UV-signature mutations20, they are more common in sun-exposed skin20–23.”
From Mechanisms and prevention of <scp>UV</scp>‐induced melanoma (2018) · cites this paper as [23]
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- Authors
- Bauer, J., Büttner, P., Murali, R., Okamoto, I., Kolaitis, N. A., Landi, M. T., Scolyer, R. A., & Bastian, B. C.
- Affiliations
- University of California, San Francisco (US)
- The University of Sydney (AU)
- University of Vienna (AT)
- Division of Cancer Epidemiology and Genetics (US)
- Corresponding author
- Bastian, Boris C.
- ORCID
- Venue
- Pigment Cell & Melanoma Research
- Publisher
- Wiley
- Published
- 2011-03-10
- Volume
- 24
- Issue
- 2
- Pages
- 345-351
- ISSN
- 1755-1471 (ISSN-L)
- 1755-148X
- PMC
- PMC3107974
- OpenAlex
- W2102584939
- Cited by
- 211
- References
- 28
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 11 · 2023: 9 · 2022: 11 · 2021: 18 · 2020: 10 · 2019: 12 · 2018: 11 · 2017: 13 · 2016: 10 · 2015: 18 · 2014: 33 · 2013: 16 · 2012: 18
- FWCI
- 10.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pigment Cell & Melanoma Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ResearchOnline at James Cook University (James Cook University) (submittedVersion)
- Funders
- Curtin University of Technology
- National Cancer Institute (R01 CA1315241, R01CA131524)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- BRAF mutation, cutaneous melanoma, solar elastosis, age of onset, head and neck melanoma, melanocyte origin, UV-induced skin damage
- MeSH terms
- Adult, Aged, DNA Mutational Analysis, Female, Humans, Male, Melanoma, Middle Aged, Mutation, Skin, Skin Neoplasms, Sunlight, Ultraviolet Rays, Multivariate Analysis, Proto-Oncogene Proteins B-raf
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