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 report two identical mutations in FGFR2 that cause craniosynostosis syndromes, Crouzon, Apert, and Pfeiffer in gastric carcinoma. A missense mutation (Ser267Pro) in exon IIIa and a splice site mutation (940-2A-->G) in exon IIIc were detected in gastric cancer patients. Interestingly, these heterozygous somatic mutations are identical to the germinal activating mutations in FGFR2 reported previously in craniosynostosis syndromes. In addition, the two novel mutations of FGFR3 in colorectal carcinomas were identified. All identified mutations occurred at highly conserved sequences, not only in the FGFR family of molecules, but also throughout evolution and clustered in the immunoglobulin-like loop-III domain, highlighting the functional importance of this domain. Our results indicate that FGFR2 and FGFR3, in addition to their potential role in skeletal dysplasias, play an important role in tumorigenesis.
Jang
J H
JH
Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744, Korea.
Shin
K H
KH
Park
J G
JG
D000595:Amino Acid Sequence; D000818:Animals; D015179:Colorectal Neoplasms / Q000235:genetics*; D017124:Conserved Sequence; D003398:Craniosynostoses / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011505:Protein-Tyrosine Kinases; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*
D017468:Receptors, Fibroblast Growth Factor; C496353:FGFR2 protein, human; C496365:FGFR3 protein, human; C496354:Fgfr2 protein, mouse; C496356:Fgfr2 protein, rat; C496366:Fgfr3 protein, mouse; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3