A few cases of ESOS with MDM2 amplification have also been reported, suggesting some similarity to skeletal low-grade osteosarcoma such as parosteal osteosarcoma, where MDM2 is often amplified.
GRIM-19 was proved to modulate radiation-induced osteosarcoma cells apoptosis in a p53 dependent manner by mediating MDM2 activity, which sheds light on the development of GRIM-19-based molecular target therapy on osteosarcoma.
These mice did not develop malignancies; however, these animals and the MG63 human osteosarcoma cell line with high levels of Mdm2 showed an increase in bone mineralization.
In conclusion, these results testified that Ras-ERK1/2 signalling promoted the development of OS by mediating H4K12ac through MDM2-mediated HAT1 degradation.
We retrospectively reviewed 13 DLOS patients (six men, seven women; median age 32 years (interquartile range (IQR) 27 to 38)) diagnosed using the following criteria: the histological coexistence of low-grade and high-grade osteosarcoma components in the lesion, and positive immunohistochemistry of mouse double minute 2 homolog (MDM2) and cyclin-dependent kinase 4 (CDK4) associated with MDM2 amplification.
These findings from the study demonstrated that Ras-ERK1/2 signaling could promote the development of OS via regulating H2BK12ac through MDM2-mediated CBP degradation.