We also found that the FGFR3 S249C mutation was common in three other cancer types with an APOBEC mutational signature, but rare in urothelial tumors without APOBEC mutagenesis and in two diseases probably related to aging.
FGFR3 mutations (p.S249C) were found in 8.5% (6/71) of tumors and were significantly associated with FGFR3 protein overexpression (p < 0.001), and unfavourable clinical outcome (p = 0.001).
When the results of the FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C and in exon 10, G372C and T375C, were analyzed one by one or as a group, despite the findings of previous research reports, our data suggest that these mutations are detected homogenously regardless of the tumor classification and tumor grade.
We identified a tumour cell line, 97-7, expressing the most common FGFR3 mutation (S249C) at similar FGFR3 transcript levels to low-stage and grade tumours.
Compared to patients with wildtype FGFR3 tumor, patients with S249C FGFR3 mutated tumors were older (mean age 64 vs. 49.4 years, P = 0.02), and were more likely to be associated with a non-16/18 HPV type in their tumor.
A single nucleotide substitution at codon 249, predicting a serine to cysteine amino acid substitution (S249C) in the FGFR3 extracellular domain, was identified in one primary tumor.