The Ultraviolet Fingerprint Dominates the Mutational Spectrum of the p53 and Ha-ras Genes in Psoralen + Ultraviolet A Keratoses from Psoriasis Patients

Wolf, Peter, Kreimer-Erlacher, Heidemarie, Seidl, Hannes, Baeck, Barbara, Soyer, H. Peter and Kerl, Helmut (2004) The Ultraviolet Fingerprint Dominates the Mutational Spectrum of the p53 and Ha-ras Genes in Psoralen + Ultraviolet A Keratoses from Psoriasis Patients. Journal of Investigative Dermatology, 122 1: 190-200. doi:10.1046/j.0022-202X.2004.22118.x


Author Wolf, Peter
Kreimer-Erlacher, Heidemarie
Seidl, Hannes
Baeck, Barbara
Soyer, H. Peter
Kerl, Helmut
Title The Ultraviolet Fingerprint Dominates the Mutational Spectrum of the p53 and Ha-ras Genes in Psoralen + Ultraviolet A Keratoses from Psoriasis Patients
Journal name Journal of Investigative Dermatology   Check publisher's open access policy
ISSN 0022-202X
1523-1747
Publication date 2004-01-01
Year available 2004
Sub-type Article (original research)
DOI 10.1046/j.0022-202X.2004.22118.x
Open Access Status
Volume 122
Issue 1
Start page 190
End page 200
Total pages 11
Place of publication Baltimore Md
Publisher NPG
Language eng
Subject 110304 Dermatology
Abstract Psoriasis patients exposed to high cumulative doses of psoralen + ultraviolet A frequently exhibit so-called "psoralen + ultraviolet A keratoses" (i.e., hyperkeratotic lesions with varying degrees of histologic atypia). The exact causes and molecular mechanisms of psoralen + ultraviolet A keratoses however, are not clear. We therefore performed DNA mutational analysis of the tumor suppressor gene p53 (exons in psoralen + ultraviolet A keratoses from 10 long-term psoralen + ultraviolet A-treated psoriasis patients. We detected 39 p53 mutations in 16 of 28 psoralen + ultraviolet A keratoses (57%) and 18 Ha-ras mutations in 11 of 25 psoralen + ultraviolet A keratoses (44%). Of the 39 p53 mutations and 18 Ha-ras mutations, 22 (56%) and 13 (72%), respectively, were of the ultraviolet fingerprint type (Cright arrowT or CCright arrowTT transitions at dipyrimidine sites); 13 (33%) and two (11%), respectively, occurred at potential psoralen-binding sites (5'-TpA, 5'-TpG, or 5'-TpT DNA sequences) and were potentially psoralen + ultraviolet A induced; two (5%) and three (17%), respectively, were of ambiguous origin (ultraviolet and/or psoralen + ultraviolet A); and two (5%) and none (0%), respectively, were of the "other" type, respectively. We conclude that (1) the frequent mutation of p53 and Ha-ras may play a key part in the formation of at least some psoralen + ultraviolet A keratoses; (2) environmental and/or therapeutic ultraviolet exposure may be a major cause of psoralen + ultraviolet A keratosis as most Ha-ras and p53 mutations are induced by ultraviolet light; and (3) psoralen + ultraviolet A itself plays a smaller, though direct, role in causing these mutations.
Keyword Dermatology
Dermatology
DERMATOLOGY
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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