Linked Life Data

7636632

Source:http://linkedlifedata.com/resource/pubmed/id/7636632

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1995-9-14
pubmed:abstractText
Ultraviolet (UV) irradiation emitted by the sun has been clearly implicated as a major carcinogen in the formation of skin cancers in man. Indeed, the high levels of cutaneous tumors in xeroderma pigmentosum patients (XP) who are deficient in repair of UV-induced lesions have confirmed that DNA damage produced by sunlight is directly involved in the cancer development. The tumor suppressor gene, p53, very frequently found modified in human cancers, has proved to be a perfect target gene for correlating mutation spectra with different cancer causing agents as there are nearly 300 potential mutation sites available for analysis. In a comparative analysis of p53 mutations found in internal cancers with those in skin tumours we show here that clear differences exist between the types of spectra obtained. The specificity of UV induced mutations in skin cancers is confirmed when single and tandem mutations are compared. Most of the p53 point mutations found are GC to AT transitions both in skin and internal tumors where in the latter they are located mainly at CpG sequences probably due to the deamination of the unstable 5-MeC. Moreover, mutations are targeted at py-py sequences in over 90% of skin tumors whereas in internal cancers the distribution is proportional to the frequency of bipyrimidine sequences in the p53 gene. Most significantly, all mutations found in XP skin tumors are targeted at py-py sites and more than 50% are tandem CC to TT transitions considered as veritable signatures of UV-induced lesions. Tandem mutations are also relatively common (14%) in skin tumors from normal individuals compared to their very rare occurrence in internal malignancies (0.8%). Finally, nearly all mutations observed in XP skin tumors are due to unrepaired lesions remaining on the coding strand whereas no strand bias is seen in mutation location of internal or skin tumors from normal individuals. In fact the mutation spectrum analysed in XP skin cancers has permitted the first demonstration of the existence of preferential repair in man. In conclusion, using the p53 gene as a probe it is obvious that the mutation spectra from skin tumors are very similar to those observed in UV-treated gene targets in model systems but statistically different from those described in other types of human cancer. This has allowed us to demonstrate, without ambiguity, the major role of UV-induced DNA lesions in sunlight related skin carcinogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1011-1344
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:geneSymbol
p53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
115-24
pubmed:dateRevised
2007-7-23
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
The specificity of p53 mutation spectra in sunlight induced human cancers.
pubmed:affiliation
Laboratory of Molecular Genetics, Institut de Recherche sur le Cancer (IFC 1), Villejuif, France.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't