PT  - JOURNAL ARTICLE
AU  - Rebecca C. Hennessey
AU  - Robert L. Bowman
AU  - David A. Tallman
AU  - Tirzah J. Weiss
AU  - Emma R. Crawford
AU  - Brandon M. Murphy
AU  - Amy Webb
AU  - Souhui Zhang
AU  - Krista M. D. La Perle
AU  - Craig J. Burd
AU  - Ross L. Levine
AU  - A. Hunter Shain
AU  - Christin E. Burd
TI  - UVA and UVB elicit distinct mutational signatures in melanoma
AID  - 10.1101/778449
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 778449
4099  - http://biorxiv.org/content/early/2019/09/25/778449.short
4100  - http://biorxiv.org/content/early/2019/09/25/778449.full
AB  - It is difficult to discern the relative contributions of ultraviolet-A (UVA; 320-400nm) and ultraviolet-B (UVB; 280-320nm) radiation to human melanoma development. Here, we compared the tumorigenic consequences of a single UVA or UVB exposure in mouse models predisposed to Braf- or Nras-mutant melanoma. Exposures approximated the amount of UVA or UVB energy contained in ∼40 minutes of summer sunlight. While UVA accelerated melanoma onset in a subset of mice, UVB universally reduced tumor latency and induced gene mutations relevant to the human disease. Genomic analyses uncovered distinct mutational signatures specific to each UV spectrum. The UVB-specific signature was biased for mutations on the untranscribed DNA strand and closely mirrored mutational signatures enriched in human cutaneous melanoma. The UVA-specific signature mimicked SBS51, a mutational signature found in human uveal melanoma. Distinctions in the trinucleotide patterns of the UVA and UVB signatures suggest that cytosine deamination plays a key role in UVB-mediated melanomagenesis.