Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
New approaches to understanding p53 gene tumor mutation spectra
Section snippets
Introduction: basic features of p53 human tumor mutations
The p53 gene encodes a multi-functional transcription factor that participates in cell-cycle control, programmed cell death, senescence differentiation, development, genomic stability, DNA replication, transcription and repair [4], [5]. These activities are mediated by direct binding of the p53 tetramer to specific target sequence motifs in promoters of downstream effector genes, and by interactions between p53 and other cellular proteins [6], [7].
The specific DNA binding domain of the p53
The p53 mutation database: Pandora's box or Rosetta stone?
Although there is controversy and uncertainty in interpretation of p53 tumor spectra, evidence is unequivocal showing that mutation patterns and frequency can vary dramatically by cancer type and/or by patient exposure category [4], [13]. Particularly convincing are differences that have been corroborated by independent investigators, are supported by data from laboratory experiments, achieve statistical significance, and suggest a plausible biological explanation [3]. Three often-cited
Mutation screening technology: the DNA microchip
A major stumbling block in interpreting mutation patterns derived from inspection of the p53 database is the failure to achieve statistical significance, or reports of positive correlations that are, in fact, chance findings, both consequences of small sample size. Although the 10,000 mutations in the IARC database (Release 3, 1999) are impressive when considered as a whole, the number of mutations observed within a single tumor subclassification, and identified within a homogeneous patient
Acknowledgements
MCH thanks H. Vrieling for helpful discussion. Gene-targeting studies are supported in part by PHS R01 CA 79493-01 to MCH and ZQW.
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