Abstract 4337: Identification of novel fusion gene, PUM1-TRAF3, as potent biomarker in bile duct cancer

Background: Gene fusion occurs when a part of one gene fuses with a part of another gene by genome rearrangement and may possess oncogenic properties. Bile duct cancer (BDC) are one of the most lethal malignancy, but lack of proper diagnostic or prognostic markers. Our aim was to investigate BDC specific fusion genes found in patient9s specimens and its clinical significance. Method : We extracted total RNA from five BDC tissues and normal tissues from the same patients. RNA sequencing was performed and the result data was analyzed using ChimeraScan, Jaffa or FusionCatcher softwares to detect gene fusion. The expression of the detected novel fusion gene was confirmed by ddPCR using tissues from the operated BDC patients and its clinical significance was analyzed with medical information of the patients. Result : We found 52 BDC specific fusion genes by RNA sequencing and we identified novel BDC specific fusion gene, PUM1-TRAF3 by bioinformatics analysis. Total 55 patients with BDC who underwent curative surgery were evaluated to investigate clinical significance of PUM1-TRAF3. There were 28 patients (50.1%) who expressed PUM1-TRAF3 by ddPCR. Patients with PUM1-TRAF3 presented higher rate of female gender (57.1 vs. 25.9, p=0.019), advanced stage (25% vs. 3.7%, p=0.025) and recurrence rate (64.7 vs. 48.1%, p=0.080) compared to patients without PUM1-TRAF3. Disease free survival (DFS) was 12.1 vs. 29.8 (p=0.078) and overall survival was 26.1 vs. 36.6 (p=0.239) between the patients with PUM1-TRAF3 and without PUM1-TRAF3. In multivariated analysis by cox-regression, expression of PUM1-TRAF3 (HR 2.86, p=0.023), advanced stage (HR 2.69, p=0.041), higher CA19-9 (HR 1.00, p=0.011) and positive resection margin (HR 4.57, p=0.002) were significantly associated with short DFS.Conclusion : In this study, we identified novel BDC-specific fusion gene, PUM1-TRAF3. Expression of PUM1-TRAF3 was confirmed in patient9s tissues and associated with short DFS in operated BDC patients. PUM1-TRAF3 can be a potent biomarker in BDC. Citation Format: Dawoon E. Jung, Kahee Kim, Chanyang Kim, Soo Been Park, Jung Hyun Jo, Hee Seung Lee, Si Young Song. Identification of novel fusion gene, PUM1-TRAF3, as potent biomarker in bile duct cancer [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 4337.