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Low prevalence of p53, p16INK4aand Ha-ras tumour-specific mutations in low-graded actinic keratosis
- Source :
- British Journal of Dermatology. 156:34-39
- Publication Year :
- 2007
- Publisher :
- Oxford University Press (OUP), 2007.
-
Abstract
- Summary Background Ultraviolet radiation induces DNA damage and is the major risk factor for the development of non-melanoma skin cancer (NMSC). Different mutation rates of p53, p16INK4a and Ha-ras in cutaneous squamous cell carcinoma (SCC) and the earlier stage actinic keratosis (AK) have been reported. Objectives To assess the presence of missense mutations in hotspot exons of p53, p16INK4a and Ha-ras in low-graded AK. Patients/methods Cryo-biopsies of 75 sun-exposed AK lesions and 75 sun-shielded areas of normal skin from 75 AK patients were analysed to identify mutations in p53 (exons 7 and 8), p16INK4a (exon 2) and Ha-ras (exon 1) using polymerase chain reaction (PCR) followed by direct sequencing. As a representative subset of the specimens, ten mutation-negative AK were also micro-dissected in order to exclude the possibility that additional mutations were undetected. Results Eight missense and one nonsense point mutations were found in the 75 AK lesions examined (12%), of which seven (9%) were tumour-specific (i.e. present in AK lesions only) and two (3%) were p16INK4a mutations (i.e. also detected in normal skin). Three of the tumour-specific mutations (42%) were cytosine (C) to thymine (T) transitions at pyrimidine-rich sequences. Tumour-specific mutations were identified in 1% of p16INK4a (exon 2), 1% of Ha-ras (exon 1) and at a higher rate of 7% in p53 (exons 7 and 8), including one nonsense mutation. Conclusions The evaluation of a large number of AK specimens in this study have found a low gene mutation rate in low-graded AK lesions. p53 mutations rather than p16INK4a and/or Ha-ras mutations may be an early event in the development of AK to cutaneous SCC.
- Subjects :
- Male
Mutation rate
Skin Neoplasms
Nonsense mutation
Dermatology
Biology
Gene mutation
Polymerase Chain Reaction
Exon
CDKN2A
medicine
Humans
Point Mutation
Missense mutation
neoplasms
Cyclin-Dependent Kinase Inhibitor p16
Aged
Aged, 80 and over
Point mutation
Actinic keratosis
Keratosis
Middle Aged
Genes, p53
medicine.disease
Molecular biology
Genes, ras
Carcinoma, Squamous Cell
Female
Subjects
Details
- ISSN :
- 13652133 and 00070963
- Volume :
- 156
- Database :
- OpenAIRE
- Journal :
- British Journal of Dermatology
- Accession number :
- edsair.doi.dedup.....f329872c03bb93746220ffacfab6380a