Medizinische Universität Graz - Research portal
Selected Publication:
Kreimer-Erlacher, H; Seidl, H; Bäck, B; Cerroni, L; Kerl, H; Wolf, P.
High frequency of ultraviolet mutations at the INK4a-ARF locus in squamous cell carcinomas from psoralen-plus-ultraviolet-A-treated psoriasis patients.
J Invest Dermatol. 2003; 120(4):676-682
Doi: 10.1046/j.1523-1747.2003.12085.x
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- Leading authors Med Uni Graz
- Wolf Peter
- Co-authors Med Uni Graz
- Cerroni Lorenzo
- Kerl Helmut
- Seidl Hannes
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- Abstract:
- Squamous cell carcinomas in psoralen-plus-ultraviolet A (PUVA) treated patients frequently exhibit p53 tumor suppressor genes and Ha-ras protooncogenes that are mutated at dipyrimidine sites and carry the ultraviolet fingerprint (i.e., C-to-T or CC-to-TT transitions). To further broaden the knowledge of genetic mutations in PUVA-associated skin cancer, we used DNA sequencing analysis to study the mutational spectrum of the INK4a-ARF locus in 26 squamous cell carcinomas from 11 long-term PUVA-treated psoriasis patients and classified the mutations by origin (ultraviolet, ultraviolet and/or PUVA, or other). Nineteen INK4a-ARF missense/nonsense mutations were found in exons 1alpha, 1beta, and 2 in 11 of 26 squamous cell carcinomas (42%) from seven of 11 patients (64%). Eleven mutations (58%) were of the ultraviolet type; three (16%) were of the ultraviolet and/or PUVA type (i.e., C-to-T transitions at dipyrimidine sites opposite a 5'TpG sequence, a potential psoralen binding site); and five (26%) were of other type. Interestingly, 10 of 11 patients (91%) showed intron polymorphism C500G at the 3' untranslated region of exon 3. These data indicate that (i) INK4a-ARF mutations frequently occur in PUVA-associated squamous cell carcinomas; (ii) ultraviolet B radiation is the major cause of these mutations; and (iii) PUVA itself may play no direct role in development of most INK4a-ARF mutations.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Carcinoma, Squamous Cell - etiology
- Cyclin-Dependent Kinase Inhibitor p16 - genetics
- DNA Fingerprinting - genetics
- DNA Mutational Analysis - genetics
- Female - genetics
- Ficusin - administration and dosage
- Humans - administration and dosage
- Male - administration and dosage
- Middle Aged - administration and dosage
- Mutation - radiation effects
- PUVA Therapy - adverse effects
- Photosensitizing Agents - administration and dosage
- Polymorphism, Single-Stranded Conformational - administration and dosage
- Psoriasis - drug therapy
- Skin Neoplasms - etiology
- Tumor Suppressor Protein p14ARF - genetics
- Find related publications in this database (Keywords)
- carcinogenesis
- Ha-ras
- mutagenesis
- p53
- skin cancer