In non-invasive BC, these mutations were related to high risk and grade (p<0.0001) as well as progression to muscle-invasive disease (p=0.01), whereas FGFR3 mutations were observed in low-grade BC (p=0.02) and patients with recurrences (p=0.05).
We determined the frequency of FGFR3 mutations and P53 alterations in patients with pT1 bladder cancer and correlated these data to histopathological variables and clinical outcomes.
Recent precision medicine has shown that mutations in BC are frequently observed in FGFR3, RAS and PIK3CA genes, all of which correlate with RAS signaling networks.
Mutations in FGFR3 and PIK3CA, singly or combined with RAS and AKT1, are associated with AKT but not with MAPK pathway activation in urothelial bladder cancer.
The findings of this large study strongly support the notion that FGFR3 mutations characterize a subgroup of bladder cancers with good prognosis; patients with mutant TaG1 tumors have a higher risk of recurrence; and the F386L variant is selectively associated with low-grade tumors.
Since the initial description of activating mutations of FGFR3, there have been numerous studies confirming the frequency and spectrum of these mutations in bladder cancers of all grades and stages.
Analysing only previously reported point mutations, TERT mutations were found in 55% of patients with bladder cancer (independent of stage), FGFR3 mutations in 30% of patients with bladder cancer, PIK3CA in 14% and TP53 mutations in 12% of patients with bladder cancer.
We further demonstrate that activating mutations in FGFR3 associated with both multiple myeloma and bladder cancer can modulate expression of genes that regulate NFκB signaling, and promote both NFκB transcriptional activity and cell adhesion in a manner dependent on TAK1 expression in both cancer cell types.
The present study examined the utility of fibroblast growth factor receptor 3 (<i>FGFR3</i>) mutation status and gene expression as a prognostic marker in primary pT1 bladder cancer (BC).
We assessed the performance of associating a FGFR3 mutation assay and a DNA methylation analysis to improve bladder cancer detection and to predict disease recurrence of NMIBC patients.