Shaping genetic alterations in human cancer: the p53 mutation paradigm.
p53 mutations are found in 50% of human cancers. Molecular epidemiology has shown strong correlations between the spectrum of p53 mutations and exposure to exogenous carcinogens. This spectrum is influenced quantitatively and qualitatively by various upstream genetic filters that modulate carcinogen activation, detoxification, and/or DNA repair. In this review, we will discuss how other factors such as tissue specificity, SNP of genes associated with the p53 pathway, other genetic alterations, or p53 mutant heterogeneity can act as a second set of downstream filters that also have a profound impact on the spectrum of p53 mutations.
Soussi
Thierry
T
Université P.M. Curie, 4 place Jussieu, 75005 Paris, France. thierry.soussi@ki.se
Wiman
Klas G
KG
D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053842:Microsatellite Instability; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human