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Poster display session

4505 - Alteration of p53 mRNA expression in neuroblastoma and its impact in disease outcome

Date

11 Sep 2017

Session

Poster display session

Topics

Translational Research

Presenters

Mariia Inomistova

Citation

Annals of Oncology (2017) 28 (suppl_5): v595-v604. 10.1093/annonc/mdx391

Authors

M. Inomistova1, N. Khranovska1, O. Skachkova1, G. Klymniuk2, S. Pavlyk2

Author affiliations

  • 1 Laboratory Of Experimental Oncology, National Cancer Institute of the MPH Ukraine, 3022 - Kiev/UA
  • 2 Department Of Paediatric Oncology, National Cancer Institute of the MPH Ukraine, 3022 - Kiev/UA
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Resources

Abstract 4505

Background

Neuroblastoma is frequent childhood malignant tumor with high clinical heterogeneity. Despite the rare mutations of TP53 gene, p53-mediated pathway is often inactivated in neuroblastoma. The significance of MDM2, p53 direct antagonist, overexpression in neuroblastoma clinical course and outcome has been already established. But still remain patients with favorable clinical features and poor disease outcome.

Methods

The case group comprised 68 children with neuroblastoma (mean age: 36.7±4.7 months; primary tumors: 88%; MYCN+: 39%; MDM2 overexpressed: 70%). p53 mRNA expression level (EL) was analyzed in tumor samples with qRT-PCR and evaluated by the ΔΔCt method according to control GAPDH mRNA EL.

Results

We established that the value of p53 EL in neuroblastoma cells varied in wide limits. Significantly lower p53 EL was detected in recurrent and metastatic tumor samples comparing to primary tumors (P = 0.001). Insignificant increase of p53 EL in patients with unfavorable clinical and biological features (late occurrence age, IV stage, MYCN amplification) was observed. However, we revealed significant increase of p53 EL in MDM2 overexpressed tumors (P = 0.007). With ROC-analysis we assessed the optimal criterions for distribution of patients according to p53 expression (OC:>1.18 a.u., P = 0.04, AUC:0.69 for high and OC:

Conclusions

Regulation of p53-mediated pathway is complex and multicomponent system. Alteration of p53 EL is independent from clinical features marker of neuroblastoma. Analysis of p53/MDM2 co-expression provides the possibility for better neuroblastoma outcome prediction.

Clinical trial identification

Legal entity responsible for the study

National Cancer Institute of Ministry of Public Health of Ukraine

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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