Abstract 2654
Background
Ewing 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.
Methods
We 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.
Results
Nine 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.
Conclusions
Genes 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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Hellenic Society of Medical Oncology.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4228 - Clinical Evaluation of Drug-Eluting Bead Transcatheter Arterial Chemoembolization(D-TACE) versus Conventional TACE in Treatment of unresectable Hepatocellular Carcinoma
Presenter: Yi Chen
Session: Poster Display session 1
Resources:
Abstract
3930 - Safety profile of tepotinib in patients with advanced solid tumors: pooled analysis of phase I and II data
Presenter: Thomas Decaens
Session: Poster Display session 1
Resources:
Abstract
5373 - Drug-drug interaction profile of tepotinib with CYP3A and P-gp substrates
Presenter: Juergen Heuer
Session: Poster Display session 1
Resources:
Abstract
5455 - Bioavailability of tepotinib: impact of omeprazole and food
Presenter: Juergen Heuer
Session: Poster Display session 1
Resources:
Abstract
2618 - Tislelizumab Exposure-Response Analyses of Efficacy and Safety in Patients with Advanced Tumors
Presenter: Chi-Yuan Wu
Session: Poster Display session 1
Resources:
Abstract
2563 - Population Pharmacokinetics of Tislelizumab in Patients with Advanced Tumors
Presenter: Chi-Yuan Wu
Session: Poster Display session 1
Resources:
Abstract
2021 - The Addition of Metformin to Systemic Anticancer Therapy
Presenter: Jung Han Kim
Session: Poster Display session 1
Resources:
Abstract
5243 - Growth modulation index (GMI) as a comparative measure of clinical activity of larotrectinib versus prior systemic treatments in adult and pediatric TRK fusion cancer patients
Presenter: Antoine Italiano
Session: Poster Display session 1
Resources:
Abstract
598 - Analysis of the overall survival and main surrogates used for FDA approvals in solid and hematological malignancies.
Presenter: Maria Kleniewska-Wieczor
Session: Poster Display session 1
Resources:
Abstract
5381 - Comparison of intratumoral docetaxel exposure in cancer patients between nanoparticle entrapped docetaxel (CPC634) and conventional docetaxel (Cd): the CriTax study
Presenter: Ruben Van Eerden
Session: Poster Display session 1
Resources:
Abstract