کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10754361 | 1050354 | 2014 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Frequent mutations in NOTCH1 ligand-binding regions in Japanese oral squamous cell carcinoma
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کلمات کلیدی
EGFOSCCDFSNICDN stageNotch extracellular domainNECDHNSCCNotch1T stageTallDisease free survival - بقای آزاد بیماریoverall survival - بقای کلPoint mutation - جهش نقطهNotch intracellular domain - دامنه درون سلولی Notchepidermal growth factor - عامل رشد اپیدرمیT-cell acute lymphoblastic leukemia - لوسمی لنفوبلاستی حاد T-cellTumor stage - مرحله تومورoral squamous cell carcinoma - کارسینوم سلول سنگفرشی دهانیHead and neck squamous cell carcinoma - کارسینوم سلول سنگفرشی سر و گردن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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 GÂ >Â A transitions. In addition, median disease-free survival is significantly longer in patients with NOTCH1-mutated tumors as compared to those without the mutation (PÂ <Â 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 452, Issue 4, 3 October 2014, Pages 980-985
Journal: Biochemical and Biophysical Research Communications - Volume 452, Issue 4, 3 October 2014, Pages 980-985
نویسندگان
Ken-ichi Aoyama, Yoshihide Ota, Kagemasa Kajiwara, Noriaki Hirayama, Minoru Kimura,