期刊
NATURE
卷 586, 期 7830, 页码 600-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41586-020-2785-8
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资金
- National Cancer Institute [K22 CA217997]
- Melanoma Research Alliance
- LEO Foundation
- George and Judy Marcus Precision Medicine Fund
- National Center for Advancing Translational Sciences [TL1-TR001871, 1R35CA220481]
- National Institutes of Health through UCSF-CTSI [TL1-TR001871, 1R35CA220481]
- Mt. Zion Health Research Fund
- Dermatology Foundation
- American Federation of Aging Research
- NIH Director's Common Fund [DP5 OD019787]
- National Cancer Institute Cancer Center Support Grant [P30 CA082103]
Every cell in the human body has a unique set of somatic mutations, but it remains difficult to comprehensively genotype an individual cell(1). Here we describe ways to overcome this obstacle in the context of normal human skin, thus offering a glimpse into the genomic landscapes of individual melanocytes from human skin. As expected, sun-shielded melanocytes had fewer mutations than sun-exposed melanocytes. However, melanocytes from chronically sun-exposed skin (for example, the face) had a lower mutation burden than melanocytes from intermittently sun-exposed skin (for example, the back). Melanocytes located adjacent to a skin cancer had higher mutation burdens than melanocytes from donors without skin cancer, implying that the mutation burden of normal skin can be used to measure cumulative sun damage and risk of skin cancer. Moreover, melanocytes from healthy skin commonly contained pathogenic mutations, although these mutations tended to be weakly oncogenic, probably explaining why they did not give rise to discernible lesions. Phylogenetic analyses identified groups of related melanocytes, suggesting that melanocytes spread throughout skin as fields of clonally related cells that are invisible to the naked eye. Overall, our results uncover the genomic landscapes of individual melanocytes, providing key insights into the causes and origins of melanoma. A combination of clonal expansion and DNA amplification is used to sequence genetic material from individual melanocytes, shedding light on the mutational landscape of these cells and the development of melanomas.
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