Abstract 116: Study of TERT promoter and FGFR3 mutations in upper-tumor urothelial carcinomas

Abstract

Abstract Background: Mutations in the promoter of the telomerase reverse transcriptase (TERT) and fibroblast growth factor receptor 3 (FGFR3) genes represent the most recurrent somatic alterations in urothelial carcinomas of the bladder. However, data regarding frequency and prognostic values of these alterations in upper-tumor urothelial carcinoma (UTUC) remain limited. Methods: DNA was extracted from 31 UTUC including 12 cases arising in the ureter and 19 in renal pelvis. Somatic mutations of TERT promoter and FGFR3 gene were assessed by Sanger sequencing. The generated sequences were analyzed by seqscape and mutational status of each of those genes were correlated with clinico-pathological tumor features. Disease-free survival and overall survival were estimated using the Kaplan-Meier method. Results: Median patient's age was 72 years (range: 41-83) with a male predominance (90.3%). Mutation status of TERT and FGFR3 were obtained in all tumors. Out of 31 UTUC, 81% were classified as high-grade including 56% which were muscle-invasive (≥pT2). TERT and FGFR3 mutations were detected in 19 (61%) and 14 (46%) tumors, respectively. Of note, 8 (26%) out of them harbored both mutations. In the TERT-mutated subgroup, we observed higher incidence of men as compared to TERT non-mutated subgroup (p = 0.04); in addition, we did not identify any other significant differences regarding other clinico-pathological features. This was also the case for FGFR3 mutations, although we observed a higher frequency in tumors arising in the ureter (66.6%) as compared to those located in renal pelvis (28.5%) (p = 0.11). Neither mutations of FGFR3 nor TERT were associated with progression-free survival and patient's overall survival. Conclusion: Our study identified a high rate of somatic mutations in FGFR3 and TERT which were similar between muscle-invasive and non-muscle invasive tumors as well as between tumors arising in the ureter or renal pelvis. As targeted inhibitors are being investigated in this setting, these results might have implications for patient's management. Citation Format: Roger Mouawad, Souheyla Bensalma, Xiaoping Su, Frederick Allanic, Eva Comperat, Morgan Rouprêt, JeanPhillipe Spano, Gabriel Malouf, David Khayat. Study of TERT promoter and FGFR3 mutations in upper-tumor urothelial carcinomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 116.