FGFR2 and Crouzon syndrome: The FGFR2 F276C mutation identified here from a cholangiocarcinoma was also in a single cholangiocarcinoma in the COSMIC database but has not been characterized.11,12 F276C is located in an extracellular, Ig-like C2-type 3 domain13 where ligand binding occurs.14 A different amino acid substitution at the same residue, F276V, has been reported in Crouzon syndrome.15 Modeling of WT and F276C FGFR2 showed that the extracellular receptor of FGFR2 contains an intrinsic disulfide bond between C278 and C342 in Ig3 (Fig 4A, shown in gold).