TP53 mutations and survival in squamous-cell carcinoma of the head and neck
TP53 mutations and survival in squamous-cell carcinoma of the head and neck
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DOI：
10.1056/nejmoa073770
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发表时间：
2007-12-20
影响因子：
158.5
通讯作者：
Koch, Wayne M.
中科院分区：
文献类型：
--
作者：
Poeta, M. Luana;Manola, Judith;Koch, Wayne M.
背景资料：肿瘤抑制蛋白p53的功能由于其基因TP 53的突变而被废除，是癌细胞中最常见的遗传改变之一。我们评估TP 53突变和生存的鳞状细胞癌患者的头和neck.Methods：共560例鳞状细胞癌的头和颈部谁是手术治疗的治愈意图，在我们的前瞻性多中心，7年的研究。使用Affytek p53芯片和Surveyor DNA内切酶和变性高效液相色谱法分析来自肿瘤标本的DNA中的TP 53突变。根据p53-DNA复合物的晶体结构预测的蛋白质结构的干扰程度，将突变分为破坏性和非破坏性两组。结果：420例患者中224例（53.3%）肿瘤组织中存在TP 53突变。与野生型TP 53相比，任何TP 53突变的存在都与总生存率降低相关（死亡风险比，1.4; 95%置信区间[CI]，1.1 - 1.8; P=0.009），与破坏性突变的相关性更强（风险比，1.7; 95% CI，1.3 - 2.4; P=0.009）。
Background: The abrogation of function of the tumor-suppressor protein p53 as a result of mutation of its gene, TP53, is one of the most common genetic alterations in cancer cells. We evaluated TP53 mutations and survival in patients with squamous-cell carcinoma of the head and neck.Methods: A total of 560 patients with squamous-cell carcinoma of the head and neck who were treated surgically with curative intent were enrolled in our prospective multicenter, 7-year study. TP53 mutations were analyzed in DNA from the tumor specimens with the use of the Affymetrix p53 chip and the Surveyor DNA endonuclease and denaturing high-performance liquid chromatography. Mutations were classified into two groups, disruptive and nondisruptive, according to the degree of disturbance of protein structure predicted from the crystal structure of the p53-DNA complexes. TP53 mutational status was compared with clinical outcome.Results: TP53 mutations were found in tumors from 224 of 420 patients (53.3%). As compared with wild-type TP53, the presence of any TP53 mutation was associated with decreased overall survival (hazard ratio for death, 1.4; 95% confidence interval [CI], 1.1 to 1.8; P=0.009), with an even stronger association with disruptive mutations (hazard ratio, 1.7; 95% CI, 1.3 to 2.4; P