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p53 mutations in colorectal cancer.

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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.

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Journal ArticleDOI

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

TL;DR: It is concluded that colorectal cancer is created and propagated by a small number of undifferentiated tumorigenic CD133+ cells, which should therefore be the target of future therapies.
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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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Clues to the pathogenesis of familial colorectal cancer

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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Journal ArticleDOI

Genetic alterations during colorectal-tumor development.

TL;DR: It is found that ras-gene mutations occurred in 58 percent of adenomas larger than 1 cm and in 47 percent of carcinomas, which are consistent with a model of colorectal tumorigenesis in which the steps required for the development of cancer often involve the mutational activation of an oncogene coupled with the loss of several genes that normally suppress tumors.
Journal ArticleDOI

Mutations in the p53 gene occur in diverse human tumour types

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

Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus

TL;DR: This work has studied the allelic diversity at the HLA-DQA locus and its association with the serologically defined Hla-DR and -DQ types and revealed eight alleles and three additional haplotypes.
Journal ArticleDOI

Localization of the gene for familial adenomatous polyposis on chromosome 5.

TL;DR: It is shown that the FAP gene is on chromosome 5, most probably near bands 5q21–q22, and that the same gene may be involved in both familial and non-familial cases of a given tumour.
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