Linked Life Data

1844242

Source:http://linkedlifedata.com/resource/pubmed/id/1844242

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1993-4-21
pubmed:abstractText
Approximately 4% of cytosine residues in human DNA are modified post-synthetically into 5-methylcytosine (5mC) which is the only modified base present in vertebrate DNA. The function of 5mC is not fully understood, but methylation of promoter regions is often associated with transcriptional inactivity and may be part of a gene silencing mechanism. While undermethylation of promoter regions is correlated with expression, the same does not seem to be true for the remainder of genes since many genes are expressed while containing 5mC in their coding regions. This is significant because 5mC is known to be inherently mutagenic and it has been suggested that it is responsible for 30-40% of all human germline point mutations. We have used direct genomic sequencing to examine the methylation status of CpG sequences which serve as potential methylation sites in the human p53 gene. These sites, which are known to be hotspots for mutations in several human cancers, were found to be methylated in the target human tissues examined. The results suggest that 5mC may play a substantial role as an endogenous mutagen in the p53 gene and that the generation of these mutations does not require the direct interaction of a carcinogen with DNA. We have also compared the spectrum of p53 mutations reported in the literature for various human tumors. The patterns of mutations seen in different tumor types vary considerably and 5mC contributes to 63% of point mutations in colorectal cancer but only 13% in lung cancer. Mutations in lung cancer are therefore caused by a different mechanism than colorectal cancer and this presumably requires the direct interaction of carcinogens with DNA. Assessment of the proportion of 5mC induced mutations in the p53 gene therefore allows for an estimate of the relative importance of endogenous and exogenous mechanisms of carcinogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:author
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
207-19
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
5-Methylcytosine as an endogenous mutagen in the p53 tumor suppressor gene.
pubmed:affiliation
USC/Kenneth Norris Jr. Comprehensive Cancer Center, Los Angeles 90033.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, Non-U.S. Gov't