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Cold Spring Harb Perspect Med. 2016 Jun 1;6(6). pii: a026336. doi: 10.1101/cshperspect.a026336.

The Role of MDM2 Amplification and Overexpression in Tumorigenesis.

Author information

1
Jon Oliner Consulting, Garrett Park, Maryland 20896.
2
Oncology Research, Amgen, Thousand Oaks, California 91320.

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.

PMID:
27194168
PMCID:
PMC4888815
DOI:
10.1101/cshperspect.a026336
[Indexed for MEDLINE]
Free PMC Article

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