Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families.

2.50
Hdl Handle:
http://hdl.handle.net/10541/95182
Title:
Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families.
Authors:
Varley, Jennifer; McGown, Gail; Thorncroft, Mary R; Santibanez-Koref, Mauro F; Kelsey, Anna M; Tricker, Karen J; Evans, D Gareth R; Birch, Jillian M
Abstract:
We have previously reported on the analysis of TP53 coding mutations in 12 classic Li-Fraumeni syndrome (LFS) families plus 9 families that were Li-Fraumeni-like (LFL) families (J. M. Birch et al., Cancer Res., 54: 1298-1304, 1994). Mutations were found in 6 of 12 LFS families and in 1 of 9 LFL families. We have now extended these studies to include an additional nine LFS and nine LFL families, and TP53 mutations have been detected in eight of nine LFS families and in three of nine LFL families. Six of the new mutations described here are the same as those previously identified in other Li-Fraumeni families and are missense mutations at codons 245, 248, and 273 (in two families); a nonsense mutation at codon 209; and a mutation at the splice donor site in exon 4. The other five mutations are novel germ-line mutations and include missense mutations at codons 136 and 344, a 2-bp deletion within codon 191, a splice acceptor mutation in intron 3, and a 167-bp deletion of part of exon 1 and intron 1. In addition, we have detected a codon 175 mutation in a family previously reported as TP53 negative. To summarize all of the data from the families we have studied in this and our previous report (J. M. Birch et al., Cancer Res., 54: 1298-1304, 1994), mutations have been detected in 15 of 21 LFS families (71%) and in 4 of 18 LFL families (22%). These figures are somewhat higher than those previously reported by us and others for the frequency of TP53 mutations in LFS and LFL families. This could reflect our analysis of all 11 exons of TP53, including noncoding regions, as well as the use of direct sequencing rather than other less-sensitive mutation detection methods.
Affiliation:
Cancer Research Campaign Department of Cancer Genetics, Paterson Institute for Cancer Research, Manchester, United Kingdom. clbjmv@picr.cr.man.ac.uk
Citation:
Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families. 1997, 57 (15):3245-52 Cancer Res.
Journal:
Cancer Research
Issue Date:
1-Aug-1997
URI:
http://hdl.handle.net/10541/95182
PubMed ID:
9242456
Type:
Article
Language:
en
ISSN:
0008-5472
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorVarley, Jenniferen
dc.contributor.authorMcGown, Gailen
dc.contributor.authorThorncroft, Mary Ren
dc.contributor.authorSantibanez-Koref, Mauro Fen
dc.contributor.authorKelsey, Anna Men
dc.contributor.authorTricker, Karen Jen
dc.contributor.authorEvans, D Gareth Ren
dc.contributor.authorBirch, Jillian Men
dc.date.accessioned2010-03-29T14:36:32Z-
dc.date.available2010-03-29T14:36:32Z-
dc.date.issued1997-08-01-
dc.identifier.citationGerm-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families. 1997, 57 (15):3245-52 Cancer Res.en
dc.identifier.issn0008-5472-
dc.identifier.pmid9242456-
dc.identifier.urihttp://hdl.handle.net/10541/95182-
dc.description.abstractWe have previously reported on the analysis of TP53 coding mutations in 12 classic Li-Fraumeni syndrome (LFS) families plus 9 families that were Li-Fraumeni-like (LFL) families (J. M. Birch et al., Cancer Res., 54: 1298-1304, 1994). Mutations were found in 6 of 12 LFS families and in 1 of 9 LFL families. We have now extended these studies to include an additional nine LFS and nine LFL families, and TP53 mutations have been detected in eight of nine LFS families and in three of nine LFL families. Six of the new mutations described here are the same as those previously identified in other Li-Fraumeni families and are missense mutations at codons 245, 248, and 273 (in two families); a nonsense mutation at codon 209; and a mutation at the splice donor site in exon 4. The other five mutations are novel germ-line mutations and include missense mutations at codons 136 and 344, a 2-bp deletion within codon 191, a splice acceptor mutation in intron 3, and a 167-bp deletion of part of exon 1 and intron 1. In addition, we have detected a codon 175 mutation in a family previously reported as TP53 negative. To summarize all of the data from the families we have studied in this and our previous report (J. M. Birch et al., Cancer Res., 54: 1298-1304, 1994), mutations have been detected in 15 of 21 LFS families (71%) and in 4 of 18 LFL families (22%). These figures are somewhat higher than those previously reported by us and others for the frequency of TP53 mutations in LFS and LFL families. This could reflect our analysis of all 11 exons of TP53, including noncoding regions, as well as the use of direct sequencing rather than other less-sensitive mutation detection methods.en
dc.language.isoenen
dc.subject.meshFemale-
dc.subject.meshGenes, p53-
dc.subject.meshGerm-Line Mutation-
dc.subject.meshHumans-
dc.subject.meshLi-Fraumeni Syndrome-
dc.subject.meshLinkage (Genetics)-
dc.subject.meshMale-
dc.subject.meshMutation-
dc.subject.meshPromoter Regions, Genetic-
dc.titleGerm-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Department of Cancer Genetics, Paterson Institute for Cancer Research, Manchester, United Kingdom. clbjmv@picr.cr.man.ac.uken
dc.identifier.journalCancer Researchen

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