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The genomic landscapes of individual melanocytes from human skin

Jessica Tang, Eleanor Fewings, Darwin Chang, Hanlin Zeng, Shanshan Liu, Aparna Jorapur, Rachel L. Belote, Andrew S. McNeal, Tuyet M. Tan, Iwei Yeh, Sarah T. Arron, Robert L. Judson-Torres, Boris C. Bastian and A. Hunter Shain ()
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Jessica Tang: University of California San Francisco
Eleanor Fewings: University of California San Francisco
Darwin Chang: University of California San Francisco
Hanlin Zeng: University of Utah School of Medicine
Shanshan Liu: University of California San Francisco
Aparna Jorapur: University of California San Francisco
Rachel L. Belote: University of Utah School of Medicine
Andrew S. McNeal: University of California San Francisco
Tuyet M. Tan: University of California San Francisco
Iwei Yeh: University of California San Francisco
Sarah T. Arron: University of California San Francisco
Robert L. Judson-Torres: University of Utah School of Medicine
Boris C. Bastian: University of California San Francisco
A. Hunter Shain: University of California San Francisco

Nature, 2020, vol. 586, issue 7830, 600-605

Abstract: Abstract Every cell in the human body has a unique set of somatic mutations, but it remains difficult to comprehensively genotype an individual cell1. 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.

Date: 2020
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DOI: 10.1038/s41586-020-2785-8

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