Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Science 313 (5786): 521-522

Copyright © 2006 by the American Association for the Advancement of Science

MC1R Germline Variants Confer Risk for BRAF-Mutant Melanoma

Maria Teresa Landi,1*{dagger} Jürgen Bauer,2,3* Ruth M. Pfeiffer,1 David E. Elder,4 Benjamin Hulley,1 Paola Minghetti,5 Donato Calista,5 Peter A. Kanetsky,7 Daniel Pinkel,6 Boris C. Bastian2

Abstract: Germline variants in MC1R, the gene encoding the melanocortin-1 receptor, and sun exposure increase risk for melanoma in Caucasians. The majority of melanomas that occur on skin with little evidence of chronic sun-induced damage (non-CSD melanoma) have mutations in the BRAF oncogene, whereas in melanomas on skin with marked CSD (CSD melanoma) these mutations are less frequent. In two independent Caucasian populations, we show that MC1R variants are strongly associated with BRAF mutations in non-CSD melanomas. In this tumor subtype, the risk for melanoma associated with MC1R is due to an increase in risk of developing melanomas with BRAF mutations.

1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
2 Departments of Dermatology and Pathology and Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.
3 Department of Dermatology, Eberhard Karls University, 72076 Tübingen, Germany.
4 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
5 Department of Dermatology, M. Bufalini Hospital, Cesena, 47023, Italy.
6 Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA.
7 Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: landim{at}mail.nih.gov

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Distinguishing Clinicopathologic Features of Patients with V600E and V600K BRAF-Mutant Metastatic Melanoma.
A. M. Menzies, L. E. Haydu, L. Visintin, M. S. Carlino, J. R. Howle, J. F. Thompson, R. F. Kefford, R. A. Scolyer, and G. V. Long (2012)
Clin. Cancer Res. 18, 3242-3249
   Abstract »    Full Text »    PDF »
23.14 Tumours of the skin.
E. O'Toole (2012)
OTM 5, med-9780199204854-chapter
   Abstract »    Full Text »
Molecular Characterization of Human Cutaneous Melanoma-derived Cell Lines.
Z. OGBAH, J. A. PUIG-BUTILLE, F. SIMONETTA, C. BADENAS, R. CERVERA, J. MILA, D. BENITEZ, J. MALVEHY, R. VILELLA, and S. PUIG (2012)
Anticancer Res 32, 1245-1251
   Abstract »    Full Text »    PDF »
PTEN Positively Regulates UVB-Induced DNA Damage Repair.
M. Ming, L. Feng, C. R. Shea, K. Soltani, B. Zhao, W. Han, R. C. Smart, C. S. Trempus, and Y.-Y. He (2011)
Cancer Res. 71, 5287-5295
   Abstract »    Full Text »    PDF »
Prognostic and Clinicopathologic Associations of Oncogenic BRAF in Metastatic Melanoma.
G. V. Long, A. M. Menzies, A. M. Nagrial, L. E. Haydu, A. L. Hamilton, G. J. Mann, T. M. Hughes, J. F. Thompson, R. A. Scolyer, and R. F. Kefford (2011)
J. Clin. Oncol. 29, 1239-1246
   Abstract »    Full Text »    PDF »
Functional EGFR Germline Polymorphisms May Confer Risk for EGFR Somatic Mutations in Non-Small Cell Lung Cancer, with a Predominant Effect on Exon 19 Microdeletions.
W. Liu, L. He, J. Ramirez, S. Krishnaswamy, R. Kanteti, Y.-C. Wang, R. Salgia, and M. J. Ratain (2011)
Cancer Res. 71, 2423-2427
   Abstract »    Full Text »    PDF »
BRAFV600E: Implications for Carcinogenesis and Molecular Therapy.
E. R. Cantwell-Dorris, J. J. O'Leary, and O. M. Sheils (2011)
Mol. Cancer Ther. 10, 385-394
   Abstract »    Full Text »    PDF »
Associations of Cumulative Sun Exposure and Phenotypic Characteristics with Histologic Solar Elastosis.
N. E. Thomas, A. Kricker, L. From, K. Busam, R. C. Millikan, M. E. Ritchey, B. K. Armstrong, J. Lee-Taylor, L. D. Marrett, H. Anton-Culver, et al. (2010)
Cancer Epidemiol. Biomarkers Prev. 19, 2932-2941
   Abstract »    Full Text »    PDF »
Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation.
A. L. Kadekaro, S. Leachman, R. J. Kavanagh, V. Swope, P. Cassidy, D. Supp, M. Sartor, S. Schwemberger, G. Babcock, K. Wakamatsu, et al. (2010)
FASEB J 24, 3850-3860
   Abstract »    Full Text »    PDF »
Population-based, Case-Control-Family Design to Investigate Genetic and Environmental Influences on Melanoma Risk: Australian Melanoma Family Study.
A. E. Cust, H. Schmid, J. A. Maskiell, J. Jetann, M. Ferguson, E. A. Holland, C. Agha-Hamilton, M. A. Jenkins, J. Kelly, R. F. Kefford, et al. (2009)
Am. J. Epidemiol. 170, 1541-1554
   Abstract »    Full Text »    PDF »
Use of Oral N-Acetylcysteine for Protection of Melanocytic Nevi against UV-Induced Oxidative Stress: Towards a Novel Paradigm for Melanoma Chemoprevention.
A. G. Goodson, M. A. Cotter, P. Cassidy, M. Wade, S. R. Florell, T. Liu, K. M. Boucher, and D. Grossman (2009)
Clin. Cancer Res. 15, 7434-7440
   Abstract »    Full Text »    PDF »
Transforming Growth Factor-{beta} Activation Promotes Genetic Context-Dependent Invasion of Immortalized Melanocytes.
R. S. Lo and O. N. Witte (2008)
Cancer Res. 68, 4248-4257
   Abstract »    Full Text »    PDF »
Network topology determines dynamics of the mammalian MAPK1,2 signaling network: bifan motif regulation of C-Raf and B-Raf isoforms by FGFR and MC1R.
M. Muller, M. Obeyesekere, G. B. Mills, and P. T. Ram (2008)
FASEB J 22, 1393-1403
   Abstract »    Full Text »    PDF »
Is Sunlight Important to Melanoma Causation?.
M. A. Tucker (2008)
Cancer Epidemiol. Biomarkers Prev. 17, 467-468
   Full Text »    PDF »
UV or Not UV: Metals Are The Answer.
F. L. Meyskens Jr. and M. Berwick (2008)
Cancer Epidemiol. Biomarkers Prev. 17, 268-270
   Full Text »    PDF »
Survival for Patients With Invasive Cutaneous Melanoma Among Ethnic Groups: The Effects of Socioeconomic Status and Treatment.
J. A. Zell, P. Cinar, M. Mobasher, A. Ziogas, F. L. Meyskens Jr, and H. Anton-Culver (2008)
J. Clin. Oncol. 26, 66-75
   Abstract »    Full Text »    PDF »
Identification of prostate cancer modifier pathways using parental strain expression mapping.
Q. Xu, P. K. Majumder, K. Ross, Y. Shim, T. R. Golub, M. Loda, and W. R. Sellers (2007)
PNAS 104, 17771-17776
   Abstract »    Full Text »    PDF »
CanPredict: a computational tool for predicting cancer-associated missense mutations.
J. S. Kaminker, Y. Zhang, C. Watanabe, and Z. Zhang (2007)
Nucleic Acids Res. 35, W595-W598
   Abstract »    Full Text »    PDF »
Number of Nevi and Early-Life Ambient UV Exposure Are Associated with BRAF-Mutant Melanoma.
N. E. Thomas, S. N. Edmiston, A. Alexander, R. C. Millikan, P. A. Groben, H. Hao, D. Tolbert, M. Berwick, K. Busam, C. B. Begg, et al. (2007)
Cancer Epidemiol. Biomarkers Prev. 16, 991-997
   Abstract »    Full Text »    PDF »
Toward a Molecular Classification of Melanoma.
L. A. Fecher, S. D. Cummings, M. J. Keefe, and R. M. Alani (2007)
J. Clin. Oncol. 25, 1606-1620
   Abstract »    Full Text »    PDF »
Distinguishing Cancer-Associated Missense Mutations from Common Polymorphisms.
J. S. Kaminker, Y. Zhang, A. Waugh, P. M. Haverty, B. Peters, D. Sebisanovic, J. Stinson, W. F. Forrest, J. F. Bazan, S. Seshagiri, et al. (2007)
Cancer Res. 67, 465-473
   Abstract »    Full Text »    PDF »
Genetic Supervision of Melanoma by MC1R.
(2006)
Journal Watch Dermatology 2006, 2
   Full Text »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882