Abstract 3660: Can the presence of fusion genes in circulating cell-free DNA serve as potential biomarkers for Ewing's sarcoma

Abstract

Abstract Background: Circulating cell-free DNA (cfDNA) is fragmented DNA derived from tumors that circulates in the blood of patients. With liquid biopsy, cfDNA has the potential to be used to monitor tumor burden in real time. Most reports have described that tumor-specific alterations in cfDNA are mutations, although little has been reported for the detection of tumor specific gene fusions. The objective of this study was to identify whether cfDNA can be used to detect tumor specific gene fusions and whether this would reflect the tumor burden of patients with Ewing's sarcoma. Patients and Methods: Multiplex long-range genomic PCR was performed to detect patient-specific genomic breakpoints in eight patients. Probes for digital PCR were designed based on the genomic breakpoint of each patient. cfDNA was extracted from the serum of patients, which was drawn at multiple time-points (pretreatment, completion of the treatment, and/or relapse). cfDNA quantification was performed by digital PCR (BioRad Qx-200). Results: Gene fusions in the cfDNA were detected in six (75%) of eight patients with high specificity. The relative gene fusion copy ratio (gene fusion copy number/wild KRAS copy number) was higher in the patients with M1b (extrapulmonary metastases at diagnosis) compared to the patients with M1a (pulmonary metastases at diagnosis) or M0 (no metastasis), although no significant relationship was observed between the relative gene fusion copy ratio and chemosensitivity. In each patient, the relative gene fusion copy ratio was the highest in pretreatment samples and decreased as the treatment progressed. Patients with relapse displayed an elevated relative gene fusion copy ratio in advance of clinical manifestation or elevation of lactase dehydrogenase. Conclusion: The amount of cfDNA in the serum strongly correlated with the treatment stage and would be useful as an early biomarker for Ewing's sarcoma patients. Citation Format: Shintaro Iwata, Hajime Kageyama, Tsukasa Yonemoto, Makiko Itami. Can the presence of fusion genes in circulating cell-free DNA serve as potential biomarkers for Ewing's sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3660.