Germline TP53 mutations are found in only 70% of families with the Li-Fraumeni syndrome (LFS), and with an even lower frequency in families suggestive of LFS but not meeting clinical criteria of the syndrome. Despite intense efforts, to date, no other genes have been associated with the disorder in a significant number of TP53 mutation-negative families. A search for defects in TP53 other than heterozygous missense mutations showed that neither intron variants nor sequence variants in the TP53 promoter are frequent in LFS, and multiexon deletions have been found to be responsible for LFS only in several cases. Another cancer predisposition syndrome, hereditary non-polyposis colon cancer, has been associated with epigenetic silencing of one allele of the MLH1 or MSH2 genes. This prompted us to test the methylation of the TP53 gene promoter in a set of 14 families suggestive of LFS using bisulphite sequencing of three DNA fragments from the 5' region of the gene. We found no detectable methylation at any of the CG dinucleotides tested. Thus, epigenetic silencing of the TP53 promoter is not a frequent cause of the disorder in families suggestive of LFS but with no germline mutations in the coding part of the gene.
- MeSH
- geny p53 MeSH
- lidé MeSH
- Liův-Fraumeniho syndrom genetika MeSH
- metylace DNA MeSH
- nádorový supresorový protein p53 genetika MeSH
- nádory genetika MeSH
- polymerázová řetězová reakce MeSH
- promotorové oblasti (genetika) genetika MeSH
- rodina MeSH
- sekvenční analýza DNA MeSH
- zárodečné mutace MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- apendektomie MeSH
- balneologie MeSH
- dítě MeSH
- gynekologická onemocnění terapie MeSH
- vaginitida MeSH
- zánět MeSH
- Check Tag
- dítě MeSH
- MeSH
- kardiovaskulární komplikace v těhotenství MeSH
- lidé MeSH
- prenatální péče MeSH
- Check Tag
- lidé MeSH
