Fucosylation is a crucial
oligosaccharide modification in
cancer. The known function of fucosylation in
cancer is to mediate
metastasis through
selectin ligand-dependent processes. Previously, we found complete loss of fucosylation in the
colon cancer cell line HCT116 due to a mutation in the
GDP-fucose synthetic
enzyme, GDP-mannose-4,6-dehydratase (GMDS). Loss of fucosylation led to escape of
cancer cells from
tumor immune surveillance followed by
tumor progression and
metastasis, suggesting a novel function of fucosylation in
tumor progression pathway. In the present study, we investigated the frequency of GMDS mutation in a number of clinical
colorectal cancer tissue samples: 81 samples of primary
colorectal cancer tissue and 39 samples of metastatic lesion including liver and lymph node. Four types of deletion mutation in GMDS were identified in original
cancer tissues as well as metastatic lesions. The frequency of GMDS mutation was slightly higher in metastatic lesions (12.8%, 5/39 samples) than in original
cancer tissues (8.6%, 7/81 samples). No mutation of the GMDS gene was observed in normal colon tissues surrounding
cancer tissues, suggesting that the mutation is somatic rather than in the germline. Immunohistochemical analysis revealed complete loss of fucosylation in three cases of
cancer tissue. All three cases had GMDS mutation. In one of three cases, loss of fucosylation was observed in only metastatic lesion, but not its original
colon cancer tissue. These data demonstrate involvement of GMDS mutation in the progression of
colorectal cancer.