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Atypical Lipomatous Tumor/Well-Diff Liposarcoma : MDM2 Amplification

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Molecular Pathogenesis: The majority of atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDLs) show giant marker or ring chromosomes containing amplified sequences from 12q13-15 region. This site contains several genes, including MDM2, CDK4, GLI, SAS and HMGA2. MDM2 and CDK4 are consistently amplified, whereas GLI and DDIT3 are overexpressed less frequently.

MDM2 is a nuclear phosphoprotein that blocks p53 and inhibits apoptosis. CDK4 phosphorylates RB1 protein, prevents its interaction with E2F transcription factor and allows the cell to escape G1-S checkpoint, thereby promoting cell proliferation.

MDM2 amplification is seen in 7% of all human cancers and 33% to 37% of sarcomas. Tumors overexpressing MDM2 include ALT/WDL, de-differentiated liposarcoma, intimal sarcoma, and low-grade osteosarcomas (parosteal, intramedullary).

Image source: Gambella A et al. FISH Diagnostic Assessment of MDM2 Amplification in Liposarcoma: Potential Pitfalls and Troubleshooting Recommendations. Int. J. Mol. Sci. 2023, 24, 1342.; used under Creative Common Attribution (CC BY) License 4.0

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