Chromosome instability is a predominant trait of fibroblasts from Li-Fraumeni families.

2.50
Hdl Handle:
http://hdl.handle.net/10541/93031
Title:
Chromosome instability is a predominant trait of fibroblasts from Li-Fraumeni families.
Authors:
Boyle, John M; Mitchell, Erika L D; Greaves, Martin J; Roberts, Stephen A; Tricker, K J; Burt, E; Varley, Jennifer; Birch, Jillian M; Scott, David
Abstract:
Previous work has indicated a role for p53 in cell cycle control, genomic stability and cellular responses to DNA-damaging agents. However, few data are available for human fibroblasts heterozygous for defined germline mutations in TP53. We report studies on 25 strains derived from 12 families with Li-Fraumeni syndrome (LFS) and 18 strains from normal volunteers. The families include three that are classical LFS families, but in whom no TP53 mutation has been found. In the families with mutations, increased longevity and resistance to low-dose-rate ionizing radiation showed a statistically significant association with the presence of TP53 mutations. However, not all heterozygotes had increased longevity or were radioresistant, and fibroblasts from cancer-affected members of LFS families without TP53 mutations showed no significant increase in either of these end points. In contrast, all mutation-carrying strains showed evidence of genomic instability, expressed as aneuploidy, and accumulated structural chromosome aberrations in up to 100% of cells, usually accompanied by loss of the wild-type TP53 allele, immediately before senescence. Levels of aneuploidy higher than in normal cells were also observed in fibroblasts from families without TP53 mutations, suggesting that chromosome instability is a major factor in determining the cancer proneness of these families.
Affiliation:
CRC Department of Cancer Genetics, Christie CRC Research Centre, Manchester, UK.
Citation:
Chromosome instability is a predominant trait of fibroblasts from Li-Fraumeni families. 1998, 77 (12):2181-92 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
Jun-1998
URI:
http://hdl.handle.net/10541/93031
PubMed ID:
9649131
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBoyle, John Men
dc.contributor.authorMitchell, Erika L Den
dc.contributor.authorGreaves, Martin Jen
dc.contributor.authorRoberts, Stephen Aen
dc.contributor.authorTricker, K Jen
dc.contributor.authorBurt, Een
dc.contributor.authorVarley, Jenniferen
dc.contributor.authorBirch, Jillian Men
dc.contributor.authorScott, Daviden
dc.date.accessioned2010-02-25T12:24:26Z-
dc.date.available2010-02-25T12:24:26Z-
dc.date.issued1998-06-
dc.identifier.citationChromosome instability is a predominant trait of fibroblasts from Li-Fraumeni families. 1998, 77 (12):2181-92 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid9649131-
dc.identifier.urihttp://hdl.handle.net/10541/93031-
dc.description.abstractPrevious work has indicated a role for p53 in cell cycle control, genomic stability and cellular responses to DNA-damaging agents. However, few data are available for human fibroblasts heterozygous for defined germline mutations in TP53. We report studies on 25 strains derived from 12 families with Li-Fraumeni syndrome (LFS) and 18 strains from normal volunteers. The families include three that are classical LFS families, but in whom no TP53 mutation has been found. In the families with mutations, increased longevity and resistance to low-dose-rate ionizing radiation showed a statistically significant association with the presence of TP53 mutations. However, not all heterozygotes had increased longevity or were radioresistant, and fibroblasts from cancer-affected members of LFS families without TP53 mutations showed no significant increase in either of these end points. In contrast, all mutation-carrying strains showed evidence of genomic instability, expressed as aneuploidy, and accumulated structural chromosome aberrations in up to 100% of cells, usually accompanied by loss of the wild-type TP53 allele, immediately before senescence. Levels of aneuploidy higher than in normal cells were also observed in fibroblasts from families without TP53 mutations, suggesting that chromosome instability is a major factor in determining the cancer proneness of these families.en
dc.language.isoenen
dc.subject.meshAdolescent-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshChild-
dc.subject.meshChromosome Aberrations-
dc.subject.meshFemale-
dc.subject.meshFibroblasts-
dc.subject.meshGenes, p53-
dc.subject.meshGerm-Line Mutation-
dc.subject.meshHeterozygote-
dc.subject.meshHumans-
dc.subject.meshLi-Fraumeni Syndrome-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshPhenotype-
dc.titleChromosome instability is a predominant trait of fibroblasts from Li-Fraumeni families.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Cancer Genetics, Christie CRC Research Centre, Manchester, UK.en
dc.identifier.journalBritish Journal of Canceren

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