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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
1998-2-19
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pubmed:abstractText |
Stochastic models of tumorigenesis have been developed to investigate the implications of experimental data on tumour induction in wild-type and p53-deficient mice for tumorigenesis mechanisms. Conventional multistage models in which inactivation of each p53 allele represents a distinct stage predict excessively large numbers of tumours in p53-deficient genotypes, allowing this category of model to be rejected. Multistage multipath models, in which a p53-mediated pathway co-exists with one or more p53-independent pathways, are consistent with the data, although these models require unknown pathways and do not enable age-specific curves of tumour appearance to be computed. An alternative model that fits the data is the 'multigate' model in which tumorigenesis results from a small number of gate-pass (enabling) events independently of p53 status. The role of p53 inactivation is as a rate modifier that accelerates the gate-pass events. This model implies that wild-type p53 acts as a 'caretaker' to maintain genetic uniformity in cell populations, and that p53 inactivation increases the probability of occurrence of a viable cellular mutant by a factor of about ten. The multigate model predicts a relationship between the time pattern of tumour occurrence and tumour genotype that should be experimentally testable. Stochastic modelling may help to distinguish 'gatekeeper' and 'caretaker' genes in other tumorigenic pathays.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-1313509,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-1356076,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-1525830,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-1552940,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-1614522,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-1905840,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-2039987,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-5279523,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-6941039,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-7546219,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-7549221,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-7550317,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-7641208,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-7667322,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-7671255,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-7805021,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-7922305,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-7987394,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-8041741,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-8103211,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-8194867,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-8275085,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-8290271,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-8435223,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-8489711,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-8516849,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-8601560,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-8827374,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9460995-9126728
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:status |
MEDLINE
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pubmed:issn |
0007-0920
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
77
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
243-52
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:9460995-Animals,
pubmed-meshheading:9460995-Gene Deletion,
pubmed-meshheading:9460995-Genes, p53,
pubmed-meshheading:9460995-Mathematics,
pubmed-meshheading:9460995-Mice,
pubmed-meshheading:9460995-Mice, Knockout,
pubmed-meshheading:9460995-Models, Biological,
pubmed-meshheading:9460995-Mutation,
pubmed-meshheading:9460995-Neoplasms, Experimental,
pubmed-meshheading:9460995-Neoplastic Stem Cells,
pubmed-meshheading:9460995-Stochastic Processes
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pubmed:year |
1998
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pubmed:articleTitle |
Stochastic modelling of tumorigenesis in p53 deficient mice.
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pubmed:affiliation |
Department of Radiation Oncology, University of Glasgow, CRC Beatson Laboratories, UK.
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pubmed:publicationType |
Journal Article
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