Molecular investigation of FGFR3 gene mutation and its correlation with clinicopathological findings in Indian bladder cancer patients

Abstract

Background: Molecular alteration of FGFR3 gene is the most common genetic event currently known in bladder cancer. Notably, FGFR3 mutation has emerged as a promising molecular biomarker for recurrence, prognosis, and therapeutic target in bladder cancer. Aim:The present study explored the frequency and distribution pattern of FGFR3 mutation in 100 Indian bladder cancer patients.Methods and results: Exons 7, 10, and 15 were subjected to nested PCR followed by bidirectional sequencing of the PCR products. Overall, FGFR3 gene mutations were identified in 19 bladder cancer patients (19%, 19 of 100). Most of the mutations were noted in exon 7 (15%), followed by exon 10 (4%). All mutations detected were missense in nature affecting amino acids at codons 248, 249, and 373. The S249C mutations were the most recurrent mutation seen in exon 7, while Y373C was commonly observed in exon 10. In contrast to exons 7 and 10, no mutations were seen in exon 15 in this study. Females and older age patients tend to show increased frequency of FGFR3 mutations. Furthermore, FGFR3 mutations were more common in low pathological stage (6/20 pTa and 13/71 pT1) and low-grade tumors (13/46). This predominance in low-grade tumors were significantly high in comparison to high-grade tumor (P = .04). Likewise, FGFR3 mutations were significantly higher in well-differentiated tumors (32.6%, 14/43) in comparison to moderately differentiated tumors (11.3%, 5/44), and poorly differentiated tumor (0%, 0/13) (P = .007). No other association of FGFR3 with tumor size, necrosis, and variant histology was noted. Conclusions:The current study highlights the spectrum of FGFR3 mutation in Indian patients, and the data presented here are similar to those reported from across the globe.

Role of FGFR3 in Urothelial Carcinoma

“…The role of FGFR3 in predicting the prognosis and progression remains unclear. Mutation studies done on two groups of the same have reported an association between mutations and a higher recurrence rate (Mhawech-Fauceglia P et al, Van Oers et al) (21,22, 23) , whereas others are contrary (van Rhijn BW et al, Hernández S et al) (24,25). Few studies have been done by immunohistochemistry.…”

Development and Validation of a Hypoxia-Related Signature for Predicting Survival Outcomes in Patients With Bladder Cancer

“…FGFR3 was a carcinogenic driver, and the mutation, activation, and overexpression of FGFR3 are common in bladder cancer ( Guancial et al, 2014 ; Pouessel et al, 2016 ). Ahmad once explored the frequency of FGFR3 mutation in Indian bladder cancer patients and found that FGFR3 mutations were more common in the low pathological stage and low-grade tumors ( Ahmad et al, 2018 ). Taken together, the effect caused by mutation of TP53 , RB1 , MUC16 , and FGFR3 were in accord with risks predicted by hypoxia risk scores in our study.…”

A hypoxia related long non-coding RNA signature could accurately predict survival outcomes in patients with bladder cancer

“…FGFR3 was a carcinogenic driver and the mutation, activation, and overexpression of FGFR3 was common in BC [ 53 , 54 ]. Ahmad once explored the frequency of FGFR3 mutation in Indian BC patients and found that FGFR3 mutations were more common in earlier pathological stage and low-grade tumors [ 55 ]. TP53 and RB1 played a role of suppressor genes in all cancer, which encoded p53 and rb1 protein involved in regulating numerous target genes.…”