Results from this study indicated that the allele-A and genotype-AA of MDM2 c.346G>A genetic variant could be an increased risk factor for the susceptibility to osteosarcoma and might be used as a potential molecular marker for evaluating the risk of osteosarcoma.
Results from this study suggest that MDM2 genetic variants are potentially related to OS susceptibility in Chinese Han population, and might be used as molecular markers for assessing OS susceptibility.
The study provides evidence supporting the association of MDM2 SNP309 with high-grade osteosarcoma risk in females and shows that TP53 Arg72Pro has a prognostic value for overall survival and EFS in osteosarcoma patients.
In conclusion, the present meta-analysis indicates that MDM2rs1690916 and rs2279744cannot be considered as genetic risk factors for OS susceptibility in the different populations.
In conclusion, these results testified that Ras-ERK1/2 signalling promoted the development of OS by mediating H4K12ac through MDM2-mediated HAT1 degradation.
Five fibroblastic high-grade osteosarcoma subtypes showed MDM2 amplification, including 2 with a microscopic appearance of high-grade osteosarcoma with part low-grade osteosarcoma (differentiated/dedifferentiated osteosarcoma) and MDM2 overexpression.
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.
Alterations of the p53/MDM2 pathway are frequent in OS and usually represent mutually exclusive tumorigenic events. p53 does not appear to be a major determinant of proliferative rate in OS.
On the other hand, late events such as the loss of RB1 and gain of MDM2, crucial regulators of cell cycle, appear to be related to the final mechanisms contributing to the metastatic establishment of osteosarcoma.
The different patterns of gene amplification and overexpression of CDK4, SAS and MDM2 in parosteal and intramedullary osteosarcomas may help explain the disparity in the biological behaviour of these two types of osteosarcoma.
Using the SJSA-1 osteosarcoma cell line which harbors an amplified MDM2 gene and wild-type p53, we have investigated the acquired resistance mechanisms both in vitro and in vivo to SAR405838.
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.
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.
Therefore, when compared with low-grade central and parosteal osteosarcomas, MDM2 and CDK4 markers cannot be used diagnostically to differentiate this subtype of osteosarcoma.