| RRC ID |
45298
|
| 著者 |
Aoyama K, Ota Y, Kajiwara K, Hirayama N, Kimura M.
|
| タイトル |
Frequent mutations in NOTCH1 ligand-binding regions in Japanese oral squamous cell carcinoma.
|
| ジャーナル |
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.
|
| 巻・号 |
452(4)
|
| ページ |
980-5
|
| 公開日 |
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 |
2.985
|
| 引用数 |
6
|
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
