MDM2 for the practicing pathologist: a primer

J Clin Pathol. 2023 May;76(5):285-290. doi: 10.1136/jcp-2022-208687. Epub 2023 Mar 10.

Abstract

The mouse double minute 2 (MDM2) gene is located on the long arm of chromosome 12 and is the primary negative regulator of p53. The MDM2 gene encodes an E3 ubiquitin-protein ligase that mediates the ubiquitination of p53, leading to its degradation. MDM2 enhances tumour formation by inactivating the p53 tumour suppressor protein. The MDM2 gene also has many p53-independent functions. Alterations of MDM2 may occur through various mechanisms and contribute to the pathogenesis of many human tumours and some non-neoplastic diseases. Detection of MDM2 amplification is used in the clinical practice setting to help diagnose multiple tumour types, including lipomatous neoplasms, low-grade osteosarcomas and intimal sarcoma, among others. It is generally a marker of adverse prognosis, and MDM2-targeted therapies are currently in clinical trials. This article provides a concise overview of the MDM2 gene and discusses practical diagnostic applications pertaining to human tumour biology.

Keywords: DIAGNOSIS; GENE AMPLIFICATION; Sarcoma.

MeSH terms

  • Humans
  • Neoplasms* / genetics
  • Pathologists
  • Proto-Oncogene Proteins c-mdm2* / genetics
  • Proto-Oncogene Proteins c-mdm2* / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitin-Protein Ligases / therapeutic use

Substances

  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Tumor Suppressor Protein p53
  • Ubiquitin-Protein Ligases