Communicated by Marc Greenblatt
Article first published online: 12 FEB 2007
This article is a US Government work and, as such, is in the public domain in the United States of America. Published in 2007 by Wiley-Liss, Inc.
Volume 28, Issue 6, pages 578–588, June 2007
How to Cite
Hocker, T. and Tsao, H. (2007), Ultraviolet radiation and melanoma: a systematic review and analysis of reported sequence variants. Hum. Mutat., 28: 578–588. doi: 10.1002/humu.20481
This article is a US Government work and, as such, is in the public domain in the United States of America.
- Issue published online: 12 APR 2007
- Article first published online: 12 FEB 2007
- Manuscript Accepted: 14 DEC 2006
- Manuscript Received: 12 JUN 2006
- National Institutes of Health (NIH)
- Department of Defense (DOD)
Despite the large body of mutational data available for melanoma and epidemiological studies linking this cancer to ultraviolet radiation (UVR), the fundamental carcinogenic mechanisms involved in melanoma remain largely unknown. To this end, we systematically reviewed, extracted, and analyzed mutational data from the extant melanoma literature in an effort to gain more insight into its early pathogenic events. We searched PubMed (1966–January 2006) using the words “mutation” AND “melanoma” in the title or abstract. Out of 2,095 returned results, there were 203 eligible studies that were subsequently analyzed. We cataloged 8,201 somatic and cultured melanoma specimens and annotated 2,041 reported somatic sequence variants. The single BRAF c.1799T>A (p.Val600Glu) alteration is the most prevalent variant while other A:T>T:A transversions were uncommon. Four highly-recurrent, non-ultraviolet B (UVB) changes account for most of the NRAS and BRAF variants. CDKN2A, PTEN/MMAC1, and TP53 harbored statistically higher rates of UVB signature changes (64.2%, 52.4%, and 69.2%, respectively) than oncogenic loci (NRAS: 15.3% and BRAF: 2.4%). More specifically, cutaneous melanomas showed a significantly higher proportion of UVB signature mutations at both TP53 and CDKN2A when compared to non-skin cancers using data from their respective locus-specific databases. Superficial spreading and nodular melanomas had the highest rates of BRAF (53.4%) and NRAS (28.0%) mutations. In melanoma, there is sufficient mutational evidence to support a role for direct UVB participation, especially at TP53 and CDKN2A. For oncogenes, the role for UVB is less clear since functionally-activating changes are uncommon and are subject to sequence constraints. Hum Mutat 28(6), 578–588, 2007. Published 2007 Wiley-Liss, Inc.