Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families.

2.50
Hdl Handle:
http://hdl.handle.net/10541/96280
Title:
Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families.
Authors:
Birch, Jillian M; Hartley, Ann L; Tricker, Karen J; Prosser, J; Condie, A; Kelsey, Anna M; Harris, Martin; Jones, P H; Binchy, Aine; Crowther, Derek; Evans, D Gareth R; Mitchell, Erika L D; Santibanez-Koref, Mauro F
Abstract:
The entire coding sequence of the p53 gene was analysed for the presence of mutations in 12 families conforming to a restricted definition of Li-Fraumeni syndrome (classic LFS) and nine families with features of LFS conforming to a broader definition. Mutations were detected in seven families. Six were point mutations with one each affecting codons 175, 180, and 220 and three affecting codon 248. The seventh was a deletion/insertion mutation in exon 4. Germline mutations in p53 were a feature of families which included children with rhabdomyosarcoma and/or adrenal cortical carcinoma. Germline p53 mutations were detected in six of the nine families with such tumors. An analysis of these 7 mutations, together with 34 published examples, showed that more than one-half were transitions at CpG dinucleotides, suggesting that the majority of germline p53 mutations may arise as a result of spontaneous events. The most common cancers occurring in the 41 families with germline p53 mutations, in common with classic LFS, were bone and soft tissue sarcoma, breast cancer, brain tumors, leukemia, and adrenocortical carcinoma, although less than one-half of the probands with germline p53 mutations came from classic LFS families. More than one-half of the cancers overall and nearly one-third of the breast cancers were diagnosed before 30 years of age. These observations have important implications for asymptomatic carriers of germline p53 mutations, and there is a need for international collaboration in the development of protocols for the management of such families.
Affiliation:
CRC Paediatric & Familial Cancer Research Group, Christie Hospital NHS Trust, Manchester, United Kingdom.
Citation:
Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families. 1994, 54 (5):1298-304 Cancer Res.
Journal:
Cancer Research
Issue Date:
1-Mar-1994
URI:
http://hdl.handle.net/10541/96280
PubMed ID:
8118819
Type:
Article
Language:
en
ISSN:
0008-5472
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBirch, Jillian Men
dc.contributor.authorHartley, Ann Len
dc.contributor.authorTricker, Karen Jen
dc.contributor.authorProsser, Jen
dc.contributor.authorCondie, Aen
dc.contributor.authorKelsey, Anna Men
dc.contributor.authorHarris, Martinen
dc.contributor.authorJones, P Hen
dc.contributor.authorBinchy, Aineen
dc.contributor.authorCrowther, Dereken
dc.contributor.authorEvans, D Gareth Ren
dc.contributor.authorMitchell, Erika L Den
dc.contributor.authorSantibanez-Koref, Mauro Fen
dc.date.accessioned2010-04-12T13:04:59Z-
dc.date.available2010-04-12T13:04:59Z-
dc.date.issued1994-03-01-
dc.identifier.citationPrevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families. 1994, 54 (5):1298-304 Cancer Res.en
dc.identifier.issn0008-5472-
dc.identifier.pmid8118819-
dc.identifier.urihttp://hdl.handle.net/10541/96280-
dc.description.abstractThe entire coding sequence of the p53 gene was analysed for the presence of mutations in 12 families conforming to a restricted definition of Li-Fraumeni syndrome (classic LFS) and nine families with features of LFS conforming to a broader definition. Mutations were detected in seven families. Six were point mutations with one each affecting codons 175, 180, and 220 and three affecting codon 248. The seventh was a deletion/insertion mutation in exon 4. Germline mutations in p53 were a feature of families which included children with rhabdomyosarcoma and/or adrenal cortical carcinoma. Germline p53 mutations were detected in six of the nine families with such tumors. An analysis of these 7 mutations, together with 34 published examples, showed that more than one-half were transitions at CpG dinucleotides, suggesting that the majority of germline p53 mutations may arise as a result of spontaneous events. The most common cancers occurring in the 41 families with germline p53 mutations, in common with classic LFS, were bone and soft tissue sarcoma, breast cancer, brain tumors, leukemia, and adrenocortical carcinoma, although less than one-half of the probands with germline p53 mutations came from classic LFS families. More than one-half of the cancers overall and nearly one-third of the breast cancers were diagnosed before 30 years of age. These observations have important implications for asymptomatic carriers of germline p53 mutations, and there is a need for international collaboration in the development of protocols for the management of such families.en
dc.language.isoenen
dc.subject.meshBase Sequence-
dc.subject.meshChild-
dc.subject.meshCodon-
dc.subject.meshExons-
dc.subject.meshFamily Health-
dc.subject.meshFemale-
dc.subject.meshGenes, p53-
dc.subject.meshHumans-
dc.subject.meshLi-Fraumeni Syndrome-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshMutation-
dc.subject.meshPedigree-
dc.subject.meshPrevalence-
dc.titlePrevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families.en
dc.typeArticleen
dc.contributor.departmentCRC Paediatric & Familial Cancer Research Group, Christie Hospital NHS Trust, Manchester, United Kingdom.en
dc.identifier.journalCancer Researchen

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