【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(cè)序能夠準(zhǔn)確、高通量地檢測(cè)基因突變情況,對(duì)惡性腫瘤治療有重要意義。本研究運(yùn)用二代基因測(cè)序(next-generation sequencing,NGS)技術(shù)檢測(cè)晚期惡性腫瘤的基因突變情況,并初步分析錯(cuò)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(nèi)科93例晚期惡性腫瘤患者病理組織石蠟標(biāo)本,利用離子個(gè)體化基因檢測(cè)儀(Ion Personal Genome Machine,Ion Torrent PGM)平臺(tái)檢測(cè)標(biāo)本16個(gè)腫瘤相關(guān)基因428個(gè)常見(jiàn)的突變位點(diǎn)的突變狀態(tài),并查詢臨床試驗(yàn)(Clinical Trails)與美國(guó)食品與藥物管理局(Food and Drug Administration,FDA)官網(wǎng)數(shù)據(jù)資料。結(jié)果共發(fā)現(xiàn)119個(gè)錯(cuò)義突變,其中TP53發(fā)生頻率最高為34.5%(41/119);除TP53突變?cè)诟髁龇N中均占較大比例外,肺癌突變頻率最高為表皮生長(zhǎng)因子受體(epidermal growth factor receptor,EGFR)25.7%(9/35),結(jié)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(cè)發(fā)現(xiàn)1個(gè)的錯(cuò)義突變位點(diǎn);93.8%(15/16)的被檢測(cè)基因有正在研發(fā)中的小分子抑制劑和(或)單抗類(lèi)制劑,75.0%(12/16)的被檢測(cè)基因已有FDA批準(zhǔn)用于特定瘤種的靶向藥物,68.8%(11/16)的被檢測(cè)基因有尚未被FDA批準(zhǔn)的靶向藥物。結(jié)論晚期惡性腫瘤基因錯(cuò)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(dǎo)的惡性腫瘤個(gè)體化靶向治療有廣闊的應(yīng)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(nèi)科;陜西省人民醫(yī)院老年呼吸內(nèi)科;
【基金】：吳階平醫(yī)學(xué)基金會(huì)臨床科研專(zhuān)項(xiàng)資助基金(320.6750.15257)
【分類(lèi)號(hào)】：R730.5
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本文編號(hào)：2261829