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
3909 - Spectrum of pathogenic germline mutations in Chinese lung cancer patients through next-generation sequencing
Presenter: Ying Huang
Session: Poster Display session 1
Resources:
Abstract
3061 - Poor prognostic impact of NTRK2 gene variation in Esophageal Squamous Cell Carcinoma
Presenter: Ye Chen
Session: Poster Display session 1
Resources:
Abstract
4735 - Mutation profile of Tibetan lung cancer revealed by Whole Exome Sequencing
Presenter: Xin Wang
Session: Poster Display session 1
Resources:
Abstract
5236 - Synergistic activity between niraparib and chemotherapy in colorectal cancer: molecular determinants from a preclinical model
Presenter: Pietro Paolo Vitiello
Session: Poster Display session 1
Resources:
Abstract
4051 - cRGDfK (cRGD) conjugated Pyropheophor¬bide-a (Pyro), a new tumor photodynamic agent, is highly accumulated and specific in tumor cell killing
Presenter: Fengwei Wang
Session: Poster Display session 1
Resources:
Abstract
859 - The expression of MMR, CD133 and the presence of p53 wt predict the response to Cabazitaxel in malignant neural tumors cell lines.
Presenter: Kevin Doello
Session: Poster Display session 1
Resources:
Abstract
2497 - IKS01, a next generation antibody drug conjugate (ADC) designed to be efficacious in tumors with low and moderate levels of folate receptor expression
Presenter: Jenny Thirlway
Session: Poster Display session 1
Resources:
Abstract
1636 - Novel Non-Camptothecin Compounds with Antiproliferative Activities against Breast Cancer Cells
Presenter: Wen-shan Li
Session: Poster Display session 1
Resources:
Abstract
3443 - Sensitization of estrogen receptor-positive breast cancer cells to tamoxifen by novel epi-oligomycin A
Presenter: Margarita Yastrebova
Session: Poster Display session 1
Resources:
Abstract
840 - Autophagy inhibition enhances leflunomide-induced cytotoxicity in human bladder cancer cells
Presenter: Li Cheng
Session: Poster Display session 1
Resources:
Abstract