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In Vitro Behavior and UV response of melanocytes derived from carriers of CDKN2A mutations and MC1R variants.

Hernando, B; Swope, VB; Guard, S; Starner, RJ; Choi, K; Anwar, A; Cassidy, P; Leachman, S; Kadekaro, AL; Bennett, DC; et al. Hernando, B; Swope, VB; Guard, S; Starner, RJ; Choi, K; Anwar, A; Cassidy, P; Leachman, S; Kadekaro, AL; Bennett, DC; Abdel-Malek, ZA (2019) In Vitro Behavior and UV response of melanocytes derived from carriers of CDKN2A mutations and MC1R variants. Pigment Cell Melanoma Res, 32 (2). pp. 259-268. ISSN 1755-148X https://doi.org/10.1111/pcmr.12732
SGUL Authors: Bennett, Dorothy Catherine

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Abstract

Co-inheritance of germline mutation in cyclin-dependent kinase inhibitor 2A (CDKN2A) and loss-of-function (LOF) melanocortin 1 receptor (MC1R) variants is clinically associated with exaggerated risk for melanoma. To understand the combined impact of these mutations, we established and tested primary human melanocyte cultures from different CDKN2A mutation carriers, expressing either wild-type MC1R or MC1R LOF variant(s). These cultures expressed the CDKN2A product p16 (INK4A) and functional MC1R. Except for 32ins24 mutant melanocytes, the remaining cultures showed no detectable aberrations in proliferation or capacity for replicative senescence. Additionally, the latter cultures responded normally to ultraviolet radiation (UV) by cell cycle arrest, JNK, p38, and p53 activation, hydrogen peroxide generation, and repair of DNA photoproducts. We propose that malignant transformation of melanocytes expressing CDKN2A mutation and MC1R LOF allele(s) requires acquisition of somatic mutations facilitated by MC1R genotype or aberrant microenvironment due to CDKN2A mutation in keratinocytes and fibroblasts. This article is protected by copyright. All rights reserved.

Item Type: Article
Additional Information: This is the peer reviewed version of the following article: Hernando B, Swope VB, Guard S, et al. In vitro behavior and UV response of melanocytes derived from carriers of CDKN2A mutations and MC1R variants. Pigment Cell Melanoma Res. 2019;32:259–268. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Keywords: CDKN2A, MC1R, proliferation, replicative senescence, ultraviolet radiation, 06 Biological Sciences, 11 Medical And Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Pigment Cell Melanoma Res
ISSN: 1755-148X
Language: eng
Dates:
DateEvent
19 February 2019Published
5 September 2018Published Online
14 August 2018Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
R21CA183440National Cancer Institutehttp://dx.doi.org/10.13039/100000054
CA130409Congressionally Directed Medical Research Programshttp://dx.doi.org/10.13039/100000090
PubMed ID: 30117292
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/110085
Publisher's version: https://doi.org/10.1111/pcmr.12732

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