An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background

Devarati Mitra, Xi Luo, Ann Morgan, Jin Wang, Mai P. Hoang, Jennifer Lo, Candace R. Guerrero, Jochen K. Lennerz, Martin C. Mihm, Jennifer A. Wargo, Kathleen C. Robinson, Suprabha P. Devi, Jillian C. Vanover, John A. D’Orazio, Martin McMahon, Marcus W. Bosenberg, Kevin M. Haigis, Daniel A. Haber, Yinsheng Wang and David E. Fisher ()
Additional contact information
Devarati Mitra: Cutaneous Biology Research Center, Massachusetts General Hospital
Xi Luo: Massachusetts General Hospital Cancer Center
Ann Morgan: Cutaneous Biology Research Center, Massachusetts General Hospital
Jin Wang: University of California
Mai P. Hoang: Massachusetts General Hospital
Jennifer Lo: Cutaneous Biology Research Center, Massachusetts General Hospital
Candace R. Guerrero: University of California
Jochen K. Lennerz: Institute of Pathology, University Ulm, Ulm 89070, Germany
Martin C. Mihm: Massachusetts General Hospital
Jennifer A. Wargo: Massachusetts General Hospital
Kathleen C. Robinson: Cutaneous Biology Research Center, Massachusetts General Hospital
Suprabha P. Devi: Cutaneous Biology Research Center, Massachusetts General Hospital
Jillian C. Vanover: Markey Cancer Center, University of Kentucky School of Medicine
John A. D’Orazio: Markey Cancer Center, University of Kentucky School of Medicine
Martin McMahon: Helen Diller Family Comprehensive Cancer Center, University of California San Francisco
Marcus W. Bosenberg: Yale University School of Medicine
Kevin M. Haigis: Massachusetts General Hospital Cancer Center
Daniel A. Haber: Massachusetts General Hospital Cancer Center
Yinsheng Wang: University of California
David E. Fisher: Cutaneous Biology Research Center, Massachusetts General Hospital

Nature, 2012, vol. 491, issue 7424, 449-453

Abstract: Individuals with the red hair/fair skin phenotype usually carry a polymorphism in the gene encoding the melanocortin 1 receptor (Mc1r) that results in the production of pigment containing a high pheomelanin-to-eumelanin ratio; here it is shown in a mouse model that inactivation of Mc1r promotes melanoma formation in the presence of the Braf oncogene, thus suggesting that pheomelanin synthesis is carcinogenic by an ultraviolet-radiation-independent mechanism.

Date: 2012
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DOI: 10.1038/nature11624

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