RRC ID 45298
Author Aoyama K, Ota Y, Kajiwara K, Hirayama N, Kimura M.
Title Frequent mutations in NOTCH1 ligand-binding regions in Japanese oral squamous cell carcinoma.
Journal Biochem. Biophys. Res. Commun.
Abstract Recent studies showed that head and neck squamous cell carcinoma (HNSCC) including oral squamous cell carcinoma (OSCC) of Caucasian, Chinese and Indian patients frequently have NOTCH1 mutations. We found eight of 84 OSCC in Japanese patients have point mutations (9.5%) correspond to the ligand binding region of NOTCH1 protein. Two set of them are the same mutations and all mutations are non-synonymous G>A transitions. In addition, median disease-free survival is significantly longer in patients with NOTCH1-mutated tumors as compared to those without the mutation (P<0.05). The protein structure simulation based on X-ray crystallography indicated that new p.A465T mutation leads to a conformational change of NOTCH1 ligand binding domain as well as the p.G481S mutant NOTCH1 with a loss of flexibility around this residue. These results suggest that NOTCH1 mutation occurs frequently in Japanese OSCC in the vicinity of the ligand binding region and, these mutations cause downregulation of the NOTCH1 function.
Volume 452(4)
Pages 980-5
Published 2014-10-3
DOI 10.1016/j.bbrc.2014.09.021
PII S0006-291X(14)01629-5
PMID 25234595
MeSH Aged Amino Acid Substitution / genetics Binding Sites / genetics Carcinoma, Squamous Cell / diagnosis Carcinoma, Squamous Cell / epidemiology* Carcinoma, Squamous Cell / genetics* Female Genetic Markers / genetics Genetic Predisposition to Disease / epidemiology Genetic Predisposition to Disease / genetics Humans Japan / epidemiology Male Models, Molecular* Mouth Neoplasms / diagnosis Mouth Neoplasms / epidemiology* Mouth Neoplasms / genetics* Mutation / genetics Polymorphism, Single Nucleotide / genetics Prevalence Protein Conformation Receptor, Notch1 / genetics* Receptor, Notch1 / ultrastructure* Reproducibility of Results Risk Factors Sensitivity and Specificity
IF 2.559
Times Cited 1
Human and Animal Cells