Erlotinib sensitivity of MAPK1p.D321N mutation in head and neck squamous cell carcinoma.
Erlotinib sensitivity of MAPK1p.D321N mutation in head and neck squamous cell carcinoma.
复制标题
头颈鳞状细胞癌中 MAPK1p.D321N 突变的厄洛替尼敏感性。
DOI：
10.1038/s41525-020-0124-5
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发表时间：
2020
影响因子：
5.3
通讯作者：
Lui,VivianWaiYan
中科院分区：
文献类型：
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作者：
Ngan,Hoi-Lam;Poon,PeonyHiuYan;Su,Yu-Xiong;Chan,JasonYingKuen;Lo,Kwok-Wai;Yeung,ChunKit;Liu,Yuchen;Wong,Eileen;Li,Hui;Lau,ChinWang;Piao,Wenying;Lui,VivianWaiYan
头颈部鳞状细胞癌（HNSCC）缺乏药物反应的预测生物标志物。通过靶向测序，我们在复发性HNSCC中发现了两个MAPK1突变，MAPK1p.D321N和p.R135K。我们先前报道了一个特殊的厄洛替尼反应与MAPK 1p.E322K。在此，通过计算机模拟和药物研究，我们确定了这两个与复发相关的MAPK1突变的功能。残基D321、R135和E322在3D上接近。MAPK1p.D321N在体内驱动显著的埃罗替尼敏感性，而p.R135K的作用是中等的。
Head and neck squamous cell carcinoma (HNSCC) lacks predictive biomarkers for drug responses. By targeted sequencing, we identified twoMAPK1mutations in recurrent HNSCC,MAPK1p.D321N, and p.R135K. We previously reported an exceptional erlotinib responder withMAPK1p.E322K. Here, by in silico and drug studies, we determined functions of these two recurrence-associatedMAPK1mutations. Residues D321, R135, and E322 are in 3D proximity.MAPK1p.D321N drives marked in vivo erlotinib sensitivity, while p.R135K’s effect is moderate.