Some of the genetic changes identified were in tumor suppressor genes previously identified as altered in osteosarcoma: p53 (arginine→histidine at codon 273 [R273H], R→cysteine at codon 723 [R273C], and tyrosine→C at codon 163 [Y163C]) and retinoblastoma 1 (RB1) (glutamic acid→* at codon 137 [E137*]).
On the other hand, transfection of p53-R273H into p53 null human osteosarcoma Saos-2 cells down-regulated procaspase-3 level and induced resistance to the drug toxicity and drug-induced apoptosis.
Transfection of mutant p53 (R175H) to p53-null osteosarcoma Saos-2 cells suppressed apoptosis induced by doxorubicin (DOX), cisplatin and gamma radiation.
In the present meta-analysis, we aimed to elucidate the associations of TP53 rs1042522 genetic polymorphism with the risk of osteosarcoma or Ewing sarcoma.
We found that subjects carrying rs12951053 CC genotype and rs1042522</span> GG genotype were significantly associated with risk of OS [odds ratio (OR)=1.68, 95% confidence intervals (CI): 1.05-2.68; OR=1.89, 95% CI: 1.16-3.07] compared with subjects carrying the common genotypes.
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.
These data do not indicate a strong link between variation in TP53 and OS risk, although they provide preliminary evidence of an increased risk of OS associated with variants at IVS2+38 and Pro72Arg.
The current findings demonstrated compellingly that the TP53 R337H mutation is associated not only with ACT but also with CPC and, to a lesser extent, with osteosarcoma, both of which are core-component tumors of the Li-Fraumeni syndrome.
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.
R337H has been identified in Brazilian families with Li-Fraumeni or related syndromes predisposing to cancers in childhood (ie, brain, renal, and adrenocortical carcinomas), adolescence (ie, soft tissue and bone sarcomas), and young adulthood (ie, breast cancer).
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.
These data do not indicate a strong link between variation in TP53 and OS risk, although they provide preliminary evidence of an increased risk of OS associated with variants at IVS2+38 and Pro72Arg.
These data do not indicate a strong link between variation in TP53 and OS risk, although they provide preliminary evidence of an increased risk of OS associated with variants at IVS2+38 and Pro72Arg.
Results of haplotype analysis also showed that A-G-G-A-C haplotype (rs12951053, rs1042522, rs8064946, rs9895829 and rs12602273) conferred significant decreased risk of OS (OR=0.37, 95% CI: 0.19-0.72) compared with A-C-G-A-C haplotype.
We found that subjects carrying rs12951053 CC genotype and rs1042522 GG genotype were significantly associated with risk of OS [odds ratio (OR)=1.68, 95% confidence intervals (CI): 1.05-2.68; OR=1.89, 95% CI: 1.16-3.07] compared with subjects carrying the common genotypes.
We identified a novel association between a TP53 rare variant and metastasis at diagnosis of osteosarcoma (rs1800372, odds ratio = 4.27, 95% confidence interval = 1.2 to 15.5, P = .026).