Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor receptor 3 genes associated with human gastric and colorectal cancers

Autosomal dominant disorders of skeletal and cranial development have been linked to fibroblast growth factor receptor (FGFR) 2 and FGFR3, Here we rep ort two identical mutations in FGFR2 that cause craniosynostosis syndromes, Crouzon, Apert, and Pfeiffer in gastric carcinoma. A missense mutation (Se r267Pro) in exon IIIa and a splice site mutation (940-2A-->G) in exon IIIc a ere detected in gastric cancer patients, Interestingly, these heterozygou s somatic mutations are identical to the germinal activating mutations in: FGFR2 reported previously in craniosynostosis syndromes. In addition, the t wo novel mutations of FGFR3 in colorectal carcinomas were identified, All i dentified mutations occurred at highly conserved sequences, not only in the FGFR family of molecules, but also throughout evolution and clustered in t he immunoglobulin-like loop-III domain, highlighting the functional importa nce of this domain, Our results indicate that FGFR2 and FGFR3, in addition to their potential role in skeletal dysplasias, play an important role in t umorigenesis.