Profiling cancer-related gene mutations in oral squamous cell carcinoma from Japanese patients by targeted amplicon sequencing.
Profiling cancer-related gene mutations in oral squamous cell carcinoma from Japanese patients by targeted amplicon sequencing.
复制标题
DOI：
10.18632/oncotarget.19262
复制
发表时间：
2017-08-29
期刊：
影响因子：
--
通讯作者：
Sasaki Y
中科院分区：
文献类型：
--
作者：
Nakagaki T;Tamura M;Kobashi K;Koyama R;Fukushima H;Ohashi T;Idogawa M;Ogi K;Hiratsuka H;Tokino T;Sasaki Y
体细胞突变分析是人类癌症研究中的一种标准做法，目的是识别导致治疗敏感性和耐药性的突变。我们对离子质子半导体测序仪进行了全面的基因组分析，使用了聚合酶链式反应靶标浓缩和下一代测序。对47例口腔鳞状细胞癌(OSCC)及其相应的非癌组织进行多重PCR扩增，获得409个癌相关基因编码区的靶向覆盖(覆盖区域：95.4%，1.69兆碱基的靶序列)。47例口腔鳞癌患者的体细胞突变数目为1~20个，平均7.60个。最常见的突变是TP53(61.7%)、NOTCH1(25.5%)、CDKN2A(19.1%)、SYNE1(14.9%)、PIK3CA(10.6%)、ROS1(10.6%)和TAF1L(10.6%)。我们还在基因组片段中检测到拷贝数变异(CNV)，这些片段可以从深度测序数据中复制或删除。通路分析表明，口腔鳞状细胞癌基因组中的体细胞异常主要涉及几条重要的途径，包括细胞周期调节和RTK-MAPK-PI3K。这项研究与临床诊断相结合，可以更好地选择治疗方法，并改善口腔鳞癌患者的预后。
Somatic mutation analysis is a standard practice in the study of human cancers to identify mutations that cause therapeutic sensitization and resistance. We performed comprehensive genomic analyses that used PCR target enrichment and next-generation sequencing on Ion Proton semiconductor sequencers. Forty-seven oral squamous cell carcinoma (OSCC) samples and their corresponding noncancerous tissues were used for multiplex PCR amplification to obtain targeted coverage of the entire coding regions of 409 cancer-related genes (covered regions: 95.4% of total, 1.69 megabases of target sequence). The number of somatic mutations in 47 patients with OSCC ranged from 1 to 20 with a mean of 7.60. The most frequent mutations were in TP53 (61.7%), NOTCH1 (25.5%), CDKN2A (19.1%), SYNE1 (14.9%), PIK3CA (10.6%), ROS1 (10.6%), and TAF1L (10.6%). We also detected copy number variations (CNVs) in the segments of the genome that could be duplicated or deleted from deep sequencing data. Pathway assessment showed that the somatic aberrations within OSCC genomes are mainly involved in several important pathways, including cell cycle regulation and RTK–MAPK-PI3K. This study may enable better selection of therapies and deliver improved outcomes for OSCC patients when combined with clinical diagnostics.