Comprehensive characterization of genes associated with the TP53 signal transduction pathway in various tumors.
Comprehensive characterization of genes associated with the TP53 signal transduction pathway in various tumors.
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DOI：
10.1007/s11010-017-2977-1
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发表时间：
2017-07
影响因子：
4.3
通讯作者：
Yamaguchi K
中科院分区：
文献类型：
--
作者：
Ohnami S;Ohshima K;Nagashima T;Urakami K;Shimoda Y;Saito J;Naruoka A;Hatakeyama K;Mochizuki T;Serizawa M;Ohnami S;Kusuhara M;Yamaguchi K
TP 53信号转导通路是癌症治疗的有吸引力的靶标。在这项研究中，我们对日本907名癌症患者进行了全面的分子评估，以确定TP 53通路的基因组改变。TP 53突变经常在许多癌症中检测到，除了黑色素瘤、胸腺肿瘤、胃肠道间质瘤和肾癌。TP 53家族成员TP 63和TP 73中非同义单核苷酸变异（SNV）的频率相对较低，尽管SNV频率增加的基因如下：乳腺癌中的PTEN（11.7%），胰腺癌和头颈癌中的CDKN 2A（11.1和9.6%），肝癌和食管癌中的ATM（18.0和11.1%）。突变型或野生型TP 53患者的MDM 2表达分别降低或升高。CDKN 1A表达在头颈部癌中随着突变型TP 53而增加。此外，TP 63过表达的特点是观察到鳞状细胞癌的肺，食管，和头部和颈部区域。此外，在胸腺瘤中经常观察到TP 63和TP 73的过表达。我们的研究结果揭示了TP 53通路中的一系列基因组改变，这是许多肿瘤类型的特征，这些数据可能在靶向治疗试验中有用。本文的在线版本（doi：10.1007/s11010-017-2977-1）包含补充材料，可供授权用户使用。
The TP53 signal transduction pathway is an attractive target for cancer treatments. In this study, we conducted a comprehensive molecular evaluation of 907 patients with cancer in Japan to identify genomic alterations in the TP53 pathway. TP53 mutations were frequently detected in many cancers, except melanoma, thymic tumors, gastrointestinal stromal tumors, and renal cancers. The frequencies of non-synonymous single nucleotide variants (SNVs) in the TP53 family members TP63 and TP73 were relatively low, although genes with increased frequencies of SNVs were as follows: PTEN (11.7%) in breast cancer, CDKN2A (11.1 and 9.6%) in pancreas and head and neck cancers, and ATM (18.0 and 11.1%) in liver and esophageal cancers. MDM2 expression was decreased or increased in patients with mutant or wild-type TP53, respectively. CDKN1A expression was increased with mutant TP53 in head and neck cancers. Moreover, TP63 overexpression was characteristically observed in squamous cell carcinomas of the lung, esophagus, and head and neck region. Additionally, overexpression of TP63 and TP73 was frequently observed in thymomas. Our results reveal a spectrum of genomic alterations in the TP53 pathway that is characteristic of many tumor types, and these data may be useful in the trials of targeted therapies. The online version of this article (doi:10.1007/s11010-017-2977-1) contains supplementary material, which is available to authorized users.