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dc.contributor.authorCrook, T.en_US
dc.contributor.authorBrooks, L. A.en_US
dc.contributor.authorCrossland, S.en_US
dc.contributor.authorOsin, P.en_US
dc.contributor.authorBarker, K. T.en_US
dc.contributor.authorWaller, J.en_US
dc.contributor.authorPhilp, E.en_US
dc.contributor.authorSmith, P. D.en_US
dc.contributor.authorYulug, I.en_US
dc.contributor.authorPeto, J.en_US
dc.contributor.authorParker, G.en_US
dc.contributor.authorAllday, M. J.en_US
dc.contributor.authorCrompton, M. R.en_US
dc.contributor.authorGusterson, B. A.en_US
dc.date.accessioned2016-02-08T10:44:13Z
dc.date.available2016-02-08T10:44:13Z
dc.date.issued1998en_US
dc.identifier.issn0950-9232
dc.identifier.urihttp://hdl.handle.net/11693/25402
dc.description.abstractThe status of p53 was investigated in breast tumours arising in germ-line carriers of mutant alleles of BRCA1 and BRCA2 and in a control series of sporadic breast tumours. p53 expression was detected in 20/26 (77%) BRCA1-, 10/22 (45%) BRCA2-associated and 25/72 (35%) grade-matched sporadic tumours. Analysis of p53 sequence revealed that the gene was mutant in 33/50 (66%) BRCA-associated tumours, whereas 7/20 (35%) sporadic grade-matched tumours contained p53 mutation (P < 0.05). A number of the mutations detected in the BRCA-associated tumours have not been previously described in human cancer databases, whilst others occur extremely rarely. Analysis of additional genes, p16(INK4), Ki-ras and β-globin revealed absence or very low incidence of mutations, suggesting that the higher frequency of p53 mutation in the BRCA-associated tumours does not reflect a generalized increase in susceptibility to the acquisition of somatic mutation. Furthermore, absence of frameshift mutations in the polypurine tracts present in the coding sequence of the TGF β type II receptor (TGF β IIR) and Bax implies that loss of function of BRCA1 or BRCA2 does not confer a mutator phenotype such as that found in tumours with microsatellite instability (MSI). p21(Waf1) was expressed in BRCA-associated tumours regardless of p53 status and, furthermore, some tumours expressing wild-type p53 did not express detectable p21(Waf1). These data do not support, therefore, the simple model based on studies of BRCA-/- embryos, in which mutation of p53 in BRCA-associated tumours results in loss of p21(Waf1) expression and deregulated proliferation. Rather, they imply that proliferation of such tumours will be subject to multiple mechanisms of growth regulation.en_US
dc.language.isoEnglishen_US
dc.source.titleOncogeneen_US
dc.subjectBRCA1en_US
dc.subjectBRCA2en_US
dc.subjectBreasten_US
dc.subjectFamilialen_US
dc.subjectMutation(s)en_US
dc.subjectP53en_US
dc.subjectTumouren_US
dc.subjectBeta globinen_US
dc.subjectBrca1 proteinen_US
dc.subjectBrca2 proteinen_US
dc.subjectProtein baxen_US
dc.subjectProtein p16en_US
dc.subjectProtein p21en_US
dc.subjectProtein p53en_US
dc.subjectTransforming growth factor beta receptoren_US
dc.subjectBreast tumoren_US
dc.subjectCodonen_US
dc.subjectControlled studyen_US
dc.subjectHumanen_US
dc.subjectHuman tissueen_US
dc.subjectMutation rateen_US
dc.subjectMutator geneen_US
dc.subjectOncogeneen_US
dc.subjectPriority journalen_US
dc.subjectTumor suppressor geneen_US
dc.subjectBRCA1 proteinen_US
dc.subjectBRCA2 proteinen_US
dc.subjectBreast neoplasmsen_US
dc.subjectCodonen_US
dc.subjectCyclin-Dependent kinase inhibitor p21en_US
dc.subjectCyclinsen_US
dc.subjectFemaleen_US
dc.subjectGene Expressionen_US
dc.subjectHumansen_US
dc.subjectMitosisen_US
dc.subjectMutationen_US
dc.subjectNeoplasm proteinsen_US
dc.subjectPhenotypeen_US
dc.subjectTranscription factorsen_US
dc.subjectTumor suppressor Protein p53en_US
dc.titlep53 mutation with frequent novel codons but not a mutator phenotype in BRCA1-and BRCA2-associated breast tumoursen_US
dc.typeArticleen_US
dc.citation.spage1681en_US
dc.citation.epage1689en_US
dc.citation.volumeNumber17en_US
dc.citation.issueNumber13en_US
dc.publisherNature Publishing Groupen_US


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