Oncogenic BRAF(V600E) Induces Clastogenesis and UVB Hypersensitivity

Dennis A Simpson; Nathalay Lemonie; David S Morgan; Shobhan Gaddameedhi; William K Kaufmann

doi:10.3390/cancers7020825

Oncogenic BRAF(V600E) Induces Clastogenesis and UVB Hypersensitivity

Cancers (Basel). 2015 Jun 17;7(2):1072-90. doi: 10.3390/cancers7020825.

Authors

Dennis A Simpson^{1

2}, Nathalay Lemonie³, David S Morgan⁴, Shobhan Gaddameedhi⁵, William K Kaufmann^{6

7

8}

Affiliations

¹ Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. dennis@email.unc.edu.
² Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. dennis@email.unc.edu.
³ Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. nlemoine@live.unc.edu.
⁴ Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. dscardamone@gmail.com.
⁵ Department of Experimental and Systems Pharmacology, College of Pharmacy, Washington State University, Spokane, WA 99210, USA. shobhan.gaddameedhi@wsu.edu.
⁶ Department of Pathology & Laboratory Medicine, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. wkarlk@med.unc.edu.
⁷ Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. wkarlk@med.unc.edu.
⁸ Center for Environmental Health and Susceptibility, University of North Carolina at Chapel Hill, CB7295, Chapel Hill, NC 27599, USA. wkarlk@med.unc.edu.

Abstract

The oncogenic BRAF(V600E) mutation is common in melanomas as well as moles. The roles that this mutation plays in the early events in the development of melanoma are poorly understood. This study demonstrates that expression of BRAF(V600E) is not only clastogenic, but synergizes for clastogenesis caused by exposure to ultraviolet radiation in the 300 to 320 nM (UVB) range. Expression of BRAF(V600E) was associated with induction of Chk1 pS280 and a reduction in chromatin remodeling factors BRG1 and BAF180. These alterations in the Chk1 signaling pathway and SWI/SNF chromatin remodeling pathway may contribute to the clastogenesis and UVB sensitivity. These results emphasize the importance of preventing sunburns in children with developing moles.

Keywords: BRAF(V600E); UVB; melanocytes; melanoma.

Abstract

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