title: The Role of MDM2 Amplification and Overexpression in Tumorigenesis.
abstract: Mouse double minute 2 (MDM2) is a critical negative regulator of the tumor suppressor p53, playing a key role in controlling its transcriptional activity, protein stability, and nuclear localization. MDM2 expression is up-regulated in numerous cancers, resulting in a loss of p53-dependent activities, such as apoptosis and cell-cycle arrest. Genetic amplification and inheritance of MDM2 promoter single-nucleotide polymorphisms (SNPs) are the two best-studied mechanisms for up-regulating MDM2 activity. This article provides an overview of these events in human cancer, highlighting the frequent occurrence of MDM2 amplification in sarcoma and the role of SNP309 and SNP285 in regulating MDM2 expression and cancer risk. The availability of large-scale genomic profiling datasets, like those from The Cancer Genome Atlas Research Network, have provided the opportunity to evaluate the consequences of MDM2 amplification and SNP inheritance across high-quality tumor samples from diverse cancer indications.
authors.affiliation: Jon Oliner Consulting, Garrett Park, Maryland 20896.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Oliner
authors.affiliation: Oncology Research, Amgen, Thousand Oaks, California 91320.
authors.forename: Anne Y
authors.initials: AY
authors.lastname: Saiki
authors.affiliation: Oncology Research, Amgen, Thousand Oaks, California 91320.
authors.forename: Sean
authors.initials: S
authors.lastname: Caenepeel
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005784:Gene Amplification; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2