p53 mutations in colorectal cancer.
Nanda R. Rodrigues,Andrew Rowan,M.E.F. Smith,I.B. Kerr,Walter F. Bodmer,Julian Gannon,David P. Lane +6 more
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TLDR
It is concluded that overexpression of p53 is synonymous with mutation, but some mutations would not be detected by a simple immunohistochemical analysis.Abstract:
Immunohistological staining of primary colorectal carcinomas with antibodies specific to p53 demonstrated gross overexpression of the protein in approximately 50% of the malignant tumors examined. Benign adenomas were all negative for p53 overexpression. To determine the molecular basis for this overexpression we examined p53 protein expression in 10 colorectal cancer cell lines. Six of the cell lines expressed high levels of p53 in ELISA, cell-staining, and immunoprecipitation studies. Direct sequencing and chemical-mismatch-cleavage analysis of p53 cDNA by using the polymerase chain reaction in these cell lines showed that all cell lines that expressed high levels of p53 were synthesizing mRNAs that encoded mutant p53 proteins. In two of those four cell lines where p53 expression was lower, point mutations were still detected. Thus, we conclude that overexpression of p53 is synonymous with mutation, but some mutations would not be detected by a simple immunohistochemical analysis. Mutation of the p53 gene is one of the commonest genetic changes in the development of human colorectal cancer.read more
Citations
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p53 mutations in human cancers
TL;DR: The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues as mentioned in this paper.
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Identification and expansion of human colon-cancer-initiating cells
Lucia Ricci-Vitiani,Dario Giuseppe Lombardi,Emanuela Pilozzi,Mauro Biffoni,Matilde Todaro,Cesare Peschle,Ruggero De Maria +6 more
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The p53 tumour suppressor gene
TL;DR: The cell cycle is composed of a series of steps which can be negatively or postively regulated by various factors, chief among the negative regulators is the p53 protein, which can lead to cancer.
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Epidermal growth factor-related peptides and their receptors in human malignancies
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Clues to the pathogenesis of familial colorectal cancer
Lauri A. Aaltonen,Päivi Peltomäki,Fredrick S. Leach,Pertti Sistonen,Lea Pylkkänen,Jukka-Pekka Mecklin,Heikki Järvinen,Steven M. Powell,Jin Jen,Stanley R. Hamilton,Gloria M. Petersen,Kenneth W. Kinzler,Bert Vogelstein,Albert de la Chapelle +13 more
TL;DR: Molecular features of "familial" cancers were compared with those of sporadic colon cancers, and a mechanism for familial tumorigenesis different from that mediated by classic tumor suppressor genes is suggested.
References
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TL;DR: It is suggested that most tumours with allelic deletions of chromosome 17p contain p53 point mutations resulting in amino-acid substitutions, and p53 gene mutations are clustered in four 'hot-spots' which exactly coincide with the four most highly conserved regions of the gene.
Journal ArticleDOI
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Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus
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Journal ArticleDOI
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Walter F. Bodmer,C.J. Bailey,Julia G. Bodmer,H J Bussey,A Ellis,Patricia Gorman,F. C. Lucibello,V. A. Murday,S.H. Rider,Peter J. Scambler +9 more
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