In:
Life Science Alliance, Life Science Alliance, LLC, Vol. 4, No. 9 ( 2021-09), p. e202101135-
Abstract:
BRAF -mutant melanomas are more likely than NRAS -mutant melanomas to arise in anatomical
locations protected from chronic sun damage. We hypothesized that this discrepancy in tumor location is a consequence of the differential
sensitivity of BRAF and NRAS -mutant melanocytes to ultraviolet light
(UV)-mediated carcinogenesis. We tested this hypothesis by comparing the mutagenic consequences of a single neonatal, ultraviolet-AI (UVA; 340–400
nm) or ultraviolet-B (UVB; 280–390 nm) exposure in mouse models heterozygous for mutant Braf or homozygous for mutant Nras . Tumor onset was accelerated by UVB, but
not UVA, and the resulting melanomas contained recurrent mutations affecting the RING domain of MAP3K1 and Actin-binding domain of Filamin A. Melanomas
from UVB-irradiated, Braf -mutant mice averaged
twice as many single-nucleotide variants and five times as many dipyrimidine variants than tumors from similarly irradiated Nras -mutant mice. A mutational signature
discovered in UVB-accelerated tumors mirrored COSMIC signatures associated with human skin cancer and was more prominent in Braf - than Nras -mutant murine melanomas. These data show
that a single UVB exposure yields a greater burden of mutations in murine tumors driven by oncogenic Braf.
Type of Medium:
Online Resource
ISSN:
2575-1077
DOI:
10.26508/lsa.202101135
Language:
English
Publisher:
Life Science Alliance, LLC
Publication Date:
2021
detail.hit.zdb_id:
2948687-7
Permalink
