1727P - Expression analysis of NHEJ and HR genes in Ewing sarcomas: Indications of DSB repair dysfunction

Abstract

BackgroundEwing sarcomas (ES) are malignant mesenchymal neoplasms composed of blue small round cells. Ewing sarcomas genetically are characterized mainly by the translocation t(11;22)(q24;q12), which creates EWS/FLI1 fusion gene. These translocations require Double Strand Break (DSB) formation and subsequent dysfunctional repair. BRCAness and HR deficiency have been reported in ES and clinical trials targeting DSB repair are currently ongoing. MethodsWe have studied the expression of Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR) genes in 32 cases of Ewing sarcoma. Baseline clinicopathological characteristics were recorded from the medical files. The expression of the following genes XRCC4, XRCC5, XRCC6, Pol λ, Pol m, Lig4, RAD51, RAD52, RAD54, BRCA1, BRCA2, FRANCC, FRANCD, DNMT1 and BRIT1 was analyzed with Real-Time PCR. Samples from healthy blood donors were used as controls. Statistical analysis was performed using SPSS Anova. ResultsNine genes out of the 15 studied showed statistically significant results. XRCC5, XRCC6, Polm, lig4 from the NHEJ DNA repair mechanism and RAD51, RAD52, RAD54, BRCA2 and FRANCD from the HR DNA repair mechanism were upregulated. Interestingly, several parts of both DSB repair mechanisms seem to be dysfunctional highlighting the involvement of NHEJ and HR in the oncogenesis of ES. ConclusionsGenes involved both to NHEJ and HR show statistically important differences in their expression in Ewing sarcoma tumor samples. DSB repair mechanisms seem to be upregulated in a manner that supports the reported articles implying that it could be a potentially important target for new therapeutic approach to these lethal tumors. Legal entity responsible for the studyThe authors. FundingHellenic Society of Medical Oncology. DisclosureAll authors have declared no conflicts of interest.