Abstract

Genetic alterations related to carcinogenesis, including punctual mutations, may have a potential as bladder cancer biomarker with high specificity and sensitivity. Specific acquired FGFR3 and HRAS mutations have been found to predominate in bladder cancer. The aim of this study is to determine the incidence of FGFR3 and HRAS mutations in bladder tumors in Morocco and to explore whether these molecular events can be detected in urine sediments of bladder cancer patients. In this order, DNA sequencing of both tissues and urine sediments was used to identify gene mutations. Among 42 DNA tumor specimens, FGFR3 mutations were found in 28.6%.On the sequenced exons 7 and 10 of FGFR3 gene, three different mutations were identified R248C, S249C and Y375C. Whereas, HRAS mutations were detected in 9.5% and two distinct HRAS mutations were found G12C and Q61L. FGFR3 mutations were mutually exclusive with HRAS mutations. FGFR3 mutations were predominant in low stage (p<0.001) and low grade (p=0.045) and this predominance was statistically significant. HRAS mutations were more frequent in low stage than in high stage but there is no significant association with the stage of tumors, whereas the predominance of HRAS mutations in high grade was statistically significant (p<0.001). Therefore, FGFR3 mutation may be considered as an early biomarker for bladder cancer and HRAS mutation may inform on the prognosis of this cancer. Gene mutations were also analyzed in urine and were detected in 56.25% for both FGFR3 and HRAS genes. Thus, mutation detection is feasible in urine sediments and a molecular approach will therefore increase the detection sensitivity.

Keywords: Bladder cancer; Mutations; Urine sediments; FGFR3; HRAS