晚期惡性腫瘤基因突變狀態(tài)二代測序臨床意義分析
發(fā)布時間：2018-10-10 12:50
【摘要】：目的靶向治療是晚期惡性腫瘤的重要治療方法,二代測序能夠準確、高通量地檢測基因突變情況,對惡性腫瘤治療有重要意義。本研究運用二代基因測序(next-generation sequencing,NGS)技術檢測晚期惡性腫瘤的基因突變情況,并初步分析錯義突變的臨床意義。方法 2011-09-01-2016-09-30收集陜西省人民醫(yī)院腫瘤內科93例晚期惡性腫瘤患者病理組織石蠟標本,利用離子個體化基因檢測儀(Ion Personal Genome Machine,Ion Torrent PGM)平臺檢測標本16個腫瘤相關基因428個常見的突變位點的突變狀態(tài),并查詢臨床試驗(Clinical Trails)與美國食品與藥物管理局(Food and Drug Administration,FDA)官網數據資料。結果共發(fā)現119個錯義突變,其中TP53發(fā)生頻率最高為34.5%(41/119);除TP53突變在各瘤種中均占較大比例外,肺癌突變頻率最高為表皮生長因子受體(epidermal growth factor receptor,EGFR)25.7%(9/35),結直腸癌為KRAS 31.6%(6/19),胃癌為KDR 3/6,卵巢癌為KRAS 2/7,宮頸癌為KDR 3/5。70例(75.3%,70/93)檢測發(fā)現1個的錯義突變位點;93.8%(15/16)的被檢測基因有正在研發(fā)中的小分子抑制劑和(或)單抗類制劑,75.0%(12/16)的被檢測基因已有FDA批準用于特定瘤種的靶向藥物,68.8%(11/16)的被檢測基因有尚未被FDA批準的靶向藥物。結論晚期惡性腫瘤基因錯義突變發(fā)生率較高,且不同瘤種的突變譜不同,目前基于NGS指導的惡性腫瘤個體化靶向治療有廣闊的應用前景。
[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.
【作者單位】： 陜西省人民醫(yī)院腫瘤內科;陜西省人民醫(yī)院老年呼吸內科;
【基金】：吳階平醫(yī)學基金會臨床科研專項資助基金(320.6750.15257)
【分類號】：R730.5
，
本文編號：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.
【作者單位】： 陜西省人民醫(yī)院腫瘤內科;陜西省人民醫(yī)院老年呼吸內科;
【基金】：吳階平醫(yī)學基金會臨床科研專項資助基金(320.6750.15257)
【分類號】：R730.5
，
本文編號：2261829
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