2.50
Hdl Handle:
http://hdl.handle.net/10541/82435
Title:
Identification of a rare polymorphism in the human TP53 promoter.
Authors:
Attwooll, Claire L; McGown, Gail; Thorncroft, Mary R; Stewart, Fiona J; Birch, Jillian M; Varley, Jennifer
Abstract:
The majority of families with classic Li-Fraumeni Syndrome (LFS) and a significant proportion of Li-Fraumeni-like (LFL) families have a germline mutation in the TP53 tumor suppressor gene. However around 20% of LFS and 60% of LFL families have no identifiable genetic defect in the coding region or splice junctions of TP53, and the genetic basis for cancer susceptibility in these families remains largely uncharacterized. To determine whether promoter mutations could be responsible for the Li-Fraumeni phenotype, we sequenced the TP53 promoter in index cases from members of classic LFS and LFL families without detectable TP53 mutations. We identified an identical single nucleotide deletion within the C/EBP- like site of the promoter in two out of eighteen such families (11%), compared to only one of a total of 366 control samples (0.3%). Although this result is highly significant (P=0.006, Fischer's exact test), the mutation did not affect the expression of TP53 in our hands. We provide evidence that this site is not utilized in the wild type TP53 promoter and further, that mutation of this site in LFS/LFL does not have a functional effect. We conclude that the sequence variant is a rare polymorphism arising within the TP53 promoter. However, the significantly increased frequency of this variant in LFS/LFL remains intriguing.
Affiliation:
CRC Department of Cancer Genetics, Paterson Institute for Cancer Research, Manchester, UK. cattwooll@deosrv.lar.ieo.it
Citation:
Identification of a rare polymorphism in the human TP53 promoter. 2002, 135 (2):165-72 Cancer Genet. Cytogenet.
Journal:
Cancer Genetics and Cytogenetics
Issue Date:
Jun-2002
URI:
http://hdl.handle.net/10541/82435
DOI:
10.1016/S0165-4608(01)00649-5
PubMed ID:
12127401
Type:
Article
Language:
en
ISSN:
0165-4608
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorAttwooll, Claire L-
dc.contributor.authorMcGown, Gail-
dc.contributor.authorThorncroft, Mary R-
dc.contributor.authorStewart, Fiona J-
dc.contributor.authorBirch, Jillian M-
dc.contributor.authorVarley, Jennifer-
dc.date.accessioned2009-09-24T08:25:18Z-
dc.date.available2009-09-24T08:25:18Z-
dc.date.issued2002-06-
dc.identifier.citationIdentification of a rare polymorphism in the human TP53 promoter. 2002, 135 (2):165-72 Cancer Genet. Cytogenet.en
dc.identifier.issn0165-4608-
dc.identifier.pmid12127401-
dc.identifier.doi10.1016/S0165-4608(01)00649-5-
dc.identifier.urihttp://hdl.handle.net/10541/82435-
dc.description.abstractThe majority of families with classic Li-Fraumeni Syndrome (LFS) and a significant proportion of Li-Fraumeni-like (LFL) families have a germline mutation in the TP53 tumor suppressor gene. However around 20% of LFS and 60% of LFL families have no identifiable genetic defect in the coding region or splice junctions of TP53, and the genetic basis for cancer susceptibility in these families remains largely uncharacterized. To determine whether promoter mutations could be responsible for the Li-Fraumeni phenotype, we sequenced the TP53 promoter in index cases from members of classic LFS and LFL families without detectable TP53 mutations. We identified an identical single nucleotide deletion within the C/EBP- like site of the promoter in two out of eighteen such families (11%), compared to only one of a total of 366 control samples (0.3%). Although this result is highly significant (P=0.006, Fischer's exact test), the mutation did not affect the expression of TP53 in our hands. We provide evidence that this site is not utilized in the wild type TP53 promoter and further, that mutation of this site in LFS/LFL does not have a functional effect. We conclude that the sequence variant is a rare polymorphism arising within the TP53 promoter. However, the significantly increased frequency of this variant in LFS/LFL remains intriguing.en
dc.language.isoenen
dc.subjectCultured Tumour Cellsen
dc.subject.meshBase Pair Mismatch-
dc.subject.meshDNA Mutational Analysis-
dc.subject.meshElectrophoretic Mobility Shift Assay-
dc.subject.meshFemale-
dc.subject.meshGene Expression Regulation-
dc.subject.meshGenes, p53-
dc.subject.meshHumans-
dc.subject.meshLi-Fraumeni Syndrome-
dc.subject.meshMale-
dc.subject.meshPedigree-
dc.subject.meshPolymorphism, Genetic-
dc.subject.meshPromoter Regions, Genetic-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.subject.meshTumor Cells, Cultured-
dc.titleIdentification of a rare polymorphism in the human TP53 promoter.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Cancer Genetics, Paterson Institute for Cancer Research, Manchester, UK. cattwooll@deosrv.lar.ieo.iten
dc.identifier.journalCancer Genetics and Cytogeneticsen

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