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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2004-9-27
pubmed:abstractText
Foci of normal keratinocytes overexpressing p53 protein are frequently found in normal human skin. Such epidermal p53 clones are common in chronically sun-exposed skin and have been suggested to play a role in skin cancer development. In the present study, we have analyzed the prevalence of p53 mutations in epidermal p53 clones from normal skin surrounding basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Using laser-assisted microdissection, 37 epidermal p53 clones adjacent to BCC (21) and SCC (16) were collected. Genetic analysis was performed using a multiplex/nested polymerase chain reaction followed by direct DNA sequencing of p53 exons 2-11. In total, 21 of 37 analyzed p53 clones consisted of p53-mutated keratinocytes. The identified mutations were located in p53 exons 4-8, corresponding to the sequence-specific DNA-binding domain. All mutations were missense, and 78% displayed a typical ultraviolet signature. The frequency of p53 mutations was similar in skin adjacent to BCC compared to SCC. The presented data confirm and extend previous knowledge on the genetic background of epidermal p53 clones. The mutation spectra found in epidermal p53 clones resemble that of non-melanoma skin cancer. Approximately, 40% of the epidermal p53 clones lacked an underlying p53 mutation, suggesting that other genetic events in genes up- or downstream of the p53 gene can generate foci of normal keratinocytes overexpressing p53 protein.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0906-6705
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
643-50
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15447725-Aged, pubmed-meshheading:15447725-Aged, 80 and over, pubmed-meshheading:15447725-Carcinoma, Basal Cell, pubmed-meshheading:15447725-Carcinoma, Squamous Cell, pubmed-meshheading:15447725-Clone Cells, pubmed-meshheading:15447725-Epidermis, pubmed-meshheading:15447725-Exons, pubmed-meshheading:15447725-Female, pubmed-meshheading:15447725-Genes, p53, pubmed-meshheading:15447725-Humans, pubmed-meshheading:15447725-Immunohistochemistry, pubmed-meshheading:15447725-Keratinocytes, pubmed-meshheading:15447725-Male, pubmed-meshheading:15447725-Middle Aged, pubmed-meshheading:15447725-Mutation, Missense, pubmed-meshheading:15447725-Polymerase Chain Reaction, pubmed-meshheading:15447725-Sequence Analysis, DNA, pubmed-meshheading:15447725-Skin Neoplasms, pubmed-meshheading:15447725-Sunlight, pubmed-meshheading:15447725-Ultraviolet Rays
pubmed:year
2004
pubmed:articleTitle
Mutation spectra of epidermal p53 clones adjacent to basal cell carcinoma and squamous cell carcinoma.
pubmed:affiliation
Department of Genetics and Pathology, University Hospital, Uppsala, Sweden. Helena.backvall@genpat.uu.se
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't