CHARACTERISTICS OF ALTERATIONS IN THE FGFR GENES IN BRAZILIAN PATIENTS WITH BLADDER CANCER

Bladder cancer is a complex disease associated with high mortality rates if not treated optimally, where the cytotoxic chemotherapy has been for long time the only standard-of-care treatment for advanced urothelial bladder cancer. Newly FDA (Food and Drug Administration) approved drugs were thought to predict a clinical benefit to patients with FGFR alterations, and FDS and ANVISA approved the Qiagen’s Therascreen FGFR RGQ RT-PCR Kit as a companion diagnostic for this investigation. FGFR alterations are present in around 20% of patients with recurrent and refractory bladder cancer and FGFR2/3 mutations occur in 10–20% of metastatic urothelial, where copy number variation and point mutation are the usual forms of alteration. The present study sought understand the incidence of FGFR mutations in the Brazilian patients. A total of 1155 patients with bladder cancer were included in this study. DNA and RNA from FFPE samples were extracted with the RecoverAll Total Nucleic Acid Isolation Kit. The target regions were amplified and processed for next generation sequencing (NGS) with the Oncomine Focus Assay kit through the Ion S5 System (ThermoFisher). Sequences were aligned and analyzed in Ion Torrent/Ion Reporter. In this study was identified FGFR alterations in 22.07% of patients with urothelial cancer. Of the FGFR alterations identified, the bases substitutions were the most common (73.73%), with 17 different kind of mutation in FGFR2/3 genes (A314T, Y375C, Y376C, C382R, N549T, N549K, K659R, R248C, S249C, G370C, Y373C, G380R, A391E, D641N, K650E, K650T, G697S), of which we can highlight the S249C (59.57%), Y373C (14.36%), R248C (13.83%) and G370C (2.66%). Amplifications were identified in the three gene, FGFR1 (5.49%), FGFR2 (0.39%) and FGFR3 (1.96%). Besides, only one fusion was identified in the FGFR3 gene (FGFR3:TACC3), 18.43%. Understand the frequency of these mutations, as presented herein, can highlight our perspectives for major developments in the FGFR-personalised therapy. Although of Qiagen’s Therascreen FGFR RGQ RT-PCR Kit have been approved for this type of investigation, this kit allows the investigation of only the fusions and most common mutations in the FGFR3, therefore, rare variants as identified in the present study would be lost. The application of wide NGS sequencings provides a more complete analysis and can help the discover of more targets for therapeutic in bladder cancer.