晚期恶性肿瘤基因突变状态二代测序临床意义分析
发布时间：2018-10-10 12:50
【摘要】：目的靶向治疗是晚期恶性肿瘤的重要治疗方法,二代测序能够准确、高通量地检测基因突变情况,对恶性肿瘤治疗有重要意义。本研究运用二代基因测序(next-generation sequencing,NGS)技术检测晚期恶性肿瘤的基因突变情况,并初步分析错义突变的临床意义。方法 2011-09-01-2016-09-30收集陕西省人民医院肿瘤内科93例晚期恶性肿瘤患者病理组织石蜡标本,利用离子个体化基因检测仪(Ion Personal Genome Machine,Ion Torrent PGM)平台检测标本16个肿瘤相关基因428个常见的突变位点的突变状态,并查询临床试验(Clinical Trails)与美国食品与药物管理局(Food and Drug Administration,FDA)官网数据资料。结果共发现119个错义突变,其中TP53发生频率最高为34.5%(41/119);除TP53突变在各瘤种中均占较大比例外,肺癌突变频率最高为表皮生长因子受体(epidermal growth factor receptor,EGFR)25.7%(9/35),结直肠癌为KRAS 31.6%(6/19),胃癌为KDR 3/6,卵巢癌为KRAS 2/7,宫颈癌为KDR 3/5。70例(75.3%,70/93)检测发现1个的错义突变位点;93.8%(15/16)的被检测基因有正在研发中的小分子抑制剂和(或)单抗类制剂,75.0%(12/16)的被检测基因已有FDA批准用于特定瘤种的靶向药物,68.8%(11/16)的被检测基因有尚未被FDA批准的靶向药物。结论晚期恶性肿瘤基因错义突变发生率较高,且不同瘤种的突变谱不同,目前基于NGS指导的恶性肿瘤个体化靶向治疗有广阔的应用前景。
[Abstract]:Objective targeted therapy is an important method for the treatment of advanced malignant tumors. Second generation sequencing can detect gene mutation accurately and high-throughput, which is of great significance for the treatment of malignant tumors. In this study, second generation gene sequencing (next-generation sequencing,NGS) was used to detect gene mutation in advanced malignant tumors, and the clinical significance of missense mutation was preliminarily analyzed. Methods paraffin wax specimens from 93 patients with advanced malignant tumor were collected from Department of Oncology, people's Hospital of Shaanxi Province, 2011-09-01-2016-09-30. The mutation status of 428 common mutation sites of 16 tumor-related genes was detected by ion individualized gene detector (Ion Personal Genome Machine,Ion Torrent PGM) platform. The data of clinical trial (Clinical Trails) and FDA (Food and Drug Administration,FDA website were queried. Results A total of 119 missense mutations were found, of which the highest frequency of TP53 was 34.5% (41 / 119), with the exception of TP53 mutation in all tumor species. The highest mutation frequency of lung cancer was epidermal growth factor receptor (epidermal growth factor receptor,EGFR) 25.7% (9 / 35), colorectal cancer was 31.6% (6 / 19), gastric cancer was KDR 3 / 6, ovarian cancer was KRAS 2 / 7, cervical cancer was KDR 3.5.70 cases (75.3G / 70 / 93), and 93.8% (15 / 16) of the detected genes were being detected. Of the small molecular inhibitors and / or monoclonal antibodies developed, 75.0% (12 / 16) of the tested genes have been approved by FDA for specific tumor targeting drugs, and 68.8% (11 / 16) of the detected genes have targeted drugs that have not been approved by FDA. Conclusion the incidence of gene missense mutation in advanced malignant tumors is high, and the mutation patterns of different tumor types are different. At present, individualized targeted therapy based on NGS guidance for malignant tumors has a broad application prospect.
【作者单位】： 陕西省人民医院肿瘤内科;陕西省人民医院老年呼吸内科;
【基金】：吴阶平医学基金会临床科研专项资助基金(320.6750.15257)
【分类号】：R730.5
，
本文编号：2261829
[Abstract]:Objective targeted therapy is an important method for the treatment of advanced malignant tumors. Second generation sequencing can detect gene mutation accurately and high-throughput, which is of great significance for the treatment of malignant tumors. In this study, second generation gene sequencing (next-generation sequencing,NGS) was used to detect gene mutation in advanced malignant tumors, and the clinical significance of missense mutation was preliminarily analyzed. Methods paraffin wax specimens from 93 patients with advanced malignant tumor were collected from Department of Oncology, people's Hospital of Shaanxi Province, 2011-09-01-2016-09-30. The mutation status of 428 common mutation sites of 16 tumor-related genes was detected by ion individualized gene detector (Ion Personal Genome Machine,Ion Torrent PGM) platform. The data of clinical trial (Clinical Trails) and FDA (Food and Drug Administration,FDA website were queried. Results A total of 119 missense mutations were found, of which the highest frequency of TP53 was 34.5% (41 / 119), with the exception of TP53 mutation in all tumor species. The highest mutation frequency of lung cancer was epidermal growth factor receptor (epidermal growth factor receptor,EGFR) 25.7% (9 / 35), colorectal cancer was 31.6% (6 / 19), gastric cancer was KDR 3 / 6, ovarian cancer was KRAS 2 / 7, cervical cancer was KDR 3.5.70 cases (75.3G / 70 / 93), and 93.8% (15 / 16) of the detected genes were being detected. Of the small molecular inhibitors and / or monoclonal antibodies developed, 75.0% (12 / 16) of the tested genes have been approved by FDA for specific tumor targeting drugs, and 68.8% (11 / 16) of the detected genes have targeted drugs that have not been approved by FDA. Conclusion the incidence of gene missense mutation in advanced malignant tumors is high, and the mutation patterns of different tumor types are different. At present, individualized targeted therapy based on NGS guidance for malignant tumors has a broad application prospect.
【作者单位】： 陕西省人民医院肿瘤内科;陕西省人民医院老年呼吸内科;
【基金】：吴阶平医学基金会临床科研专项资助基金(320.6750.15257)
【分类号】：R730.5
，
本文编号：2261829
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