Exogenously introduced wild-type and mutant p53 have recently been reported to enhance the human epidermal growth factor receptor (EGF-R) gene promoter activity in p53-deficient Saos2 osteosarcoma cells.
Screening of 288 OS and 1,090 tumors of other types revealed evidence for TP53 rearrangements in 46 (16%) OS, while none were detected in other tumor types, indicating this rearrangement to be highly specific to OS.
The study provides evidence supporting the association of MDM2 SNP309 with high-grade osteosarcoma risk in females and shows that TP53Arg72Pro has a prognostic value for overall survival and EFS in osteosarcoma patients.
The event-free survival (EFS) was worse in Ewing sarcoma patients with p16INK4 and p14ARF mutation/deletion than in those without the mutation/deletion (P = 0.019), and EFS was worse in osteosarcoma patients with TP53 alterations than in those without TP53 alterations (P = 0.048).
This study warrants a future evaluation of this formulation for gene silencing efficiency of mutant p53 in tissue culture and animal models for the treatment of osteosarcoma.
To analyze the genetic and epigenetic alterations affecting the RB1, TP53, p16INK4, and p21WAF1 tumor suppressor genes, loss of heterozygosity (LOH) at 3q and 18q, and the clinical variables of a series of Spanish children with osteosarcoma.
The tumors in Ptprz1-deficient Trp53-heterozygous mice were present in different locations (spine, long bones, ribs), and their OS nature was confirmed by undecalcified histology.
Overexpression of COPS3 has been linked to TP53 protein degradation and, being equivalent to TP53 mutation, the induction of genomic instability, which frequently occurs in high-grade osteosarcoma.
In this study, we tested the oligomerization of p53 with mutations in the oligomerization domain, when expressed in a human osteosarcoma cell line, Saos-2, in vivo.
To address the role of p53 mutations in the development and progression of osteosarcoma, the authors analyzed specimens from 247 patients with primary localized osteosarcomas and 25 patients with osteosarcomas that were metastatic at the time of diagnosis.
Here, we established patient-derived iPSCs from a Li-Fraumeni syndrome (LFS) family and investigated the role of mutant p53 in the development of osteosarcoma (OS).
As the genes of p53 and/or retinoblastoma (Rb) are mutated in the major part of osteosarcomas (OS), we aimed to study the effect of p53 and Rb transgenes on a panel of five different osteosarcoma cell lines.
We analyzed 14 native osteosarcoma tissue samples for alterations of the tumor suppressor genes RB1 and p53 on the DNA level, and as far as possible, the RNA level.
All those cases of osteoblastic OS and MFH of bone that had p53 mutations, with the exception of one case of MFH of bone that had a silent mutation, showed aggressive biologic behavior (dead of disease within 12 mo), in contrast to the MFH-like OS cases (alive without disease at 22 mo).
We and others have previously described murine models of osteosarcoma based on osteoblast-restricted Cre:lox deletion of Trp53 (p53) and Rb1 (Rb), resulting in a phenotype most similar to fibroblastic osteosarcoma in humans.
Pediatric oncologists were e-mailed an anonymous 18-question survey assessing their willingness to offer TP53 germline testing to a child with osteosarcoma with or without a family history, and they were evaluated for changes in their choices with the prior data and the new data.
Based on recommendation of the Cochrane Collaboration, this meta-analysis was conducted using data from the 17 published studies to evaluate the association of p53 alterations with clinical outcome of osteosarcoma patients.